Oh, the stains. The staaaains! It’s the stains that truly obsess Drew Barrymore.

“I’m a stan for stains,” she said on a recent episode of “The Drew Barrymore Show,” her syndicated talk show that premiered nationally in mid-September. Not that she knew what a “stan”— a portmanteau of ‘“stalker” and “fan” — actually was, which explains why she pronounced it “stand.” Whatever.

Ms. Barrymore, 45, was wearing a white lab coat over an olive green shirt, a pussy bow peeking out. Boldly labeled bottles — Laundry Detergent, Club Soda, Hand Soap, Rubbing Alcohol — were lined up on a table. As she told the audience, she’s a mother, and thus constantly rubbing, scrubbing and scouring.

This is a source of enormous pleasure. “I love concocting the perfect solutions, products, combinations, treatments, methodologies,” she said with her signature lisp. She might as well have been Carol Channing in the Gen X classic “Free to Be You and Me.”

But Ms. Barrymore wasn’t rhapsodizing about the need to share housework or the evils of advertising. Along with interior design and food, which the show also covers, stain removal is a lifelong passion. She asked viewers to send her their most aggressive soils, and she, Drew Barrymore — actress, producer, director, author, Golden Globe winner, former emancipated minor, three-time ex-wife, two-time mother, beauty entrepreneur and now host — would help them fix it.

Solving these sorts of human disasters is one of several bits on Ms. Barrymore’s sunny and frenetic show, “a jolt of optimism in a turbulent time,” as she said in a recent interview.

It was the Monday after Joe Biden’s win was announced, and Ms. Barrymore was feeling a bit wistful. People had been partying in the streets all weekend, but she and her two daughters, Olive Barrymore Kopelman, 8, and Frankie Barrymore Kopelman, 6, were out of town and missed the festivities.

“We felt like old fuddy-duddies,” she said. “We were all having FOMO. But I was also processing all weekend. I felt really internal and quiet, and I tried to think about how I could address it on the show.”

This was more challenging than it may sound, because “TDBS,” as it’s called by fans and those who produce the show, is supposed to appeal to everyone. The show is a “safe space,” and as Ms. Barrymore said in her four minute and 38 second opening monologue that morning, “I didn’t want to gloat because I know there are people out there who are hurting.”

She teared up, as she does often. Like when her ex-husband Tom Green, whom she hadn’t seen or spoken to in about 15 years, came on the show and they reminisced. Or when a psychic medium told Ms. Barrymore that Will Kopelman, to whom she was married until 2016, had relatives on the Other Side who loved her and considered her a member of the family.

Ms. Barrymore, a “little bit of a skeptic who also believes in everything,” bawled. (Mr. Kopelman later told Page Six that one of the alleged spirits was alive and well in Boston.)

She Shares, and She Cares

Ms. Barrymore, famously, is not only a crier but also a sharer, even before the sharing economy picked up online. She has always been quick to confess her fears, her insecurities; she unspools ribbons of words at record speed. In a recent Instagram post, she told her 13.6 million followers that she’s been eating her stress lately and needed a “brassiere thing” to fit into her pants. “For anyone who has to put an extender on your pants, well, just know — I feel ya,” she said.

She’s empathetic in person, too. And sweet.

I told her that my sister had died in March, and after watching the psychic episode I wanted to know what she thought. On a scale of 1 to 10, how high was the BS factor? Ms. Barrymore was shrewd enough not to respond directly: “I’d like to know what you think,” she said.

I told her I couldn’t get an appointment until October 2022. She immediately offered to call the medium on my behalf, and despite my protests — she had a million things to worry about besides helping me check in with the dead — she insisted.

“I’m the one who offered,” she said. “I really genuinely mean it. Let me please get you in touch. And I would love to know what you think. OK?”

A few hours later an email popped up from the psychic and we scheduled a session. (For what it’s worth, I think she’s an amazingly gifted … Googler).

During another conversation, Ms. Barrymore was feeling anxious. “I’m coming down after a four-hour panic attack, which is awesome,” she said. “Work and life and everything sort of collided today. It’s like I felt somehow slightly paralyzed.

“It’s hard to do it all,” she continued. “I felt like a complete failure today. Sometimes I feel like I can take on the world and today, actually, I do not feel that way at all.”

Candor has long come naturally to Ms. Barrymore. A native Angeleno, she moved to New York six years ago with Mr. Kopelman, an art adviser. They had married in 2012 in a “very Jewish” ceremony; their children are being raised Jewish, although Ms. Barrymore didn’t officially convert. But she celebrates all the holidays, which makes her … Drewish?

Moving to New York was jarring. East Coast winters felt brutal. And then, in 2016, just when she was kind of getting used to it, she and Mr. Kopelman divorced.

“Nothing I’ve ever been through compared to this divorce,” she said. “This was the first big thing that I went through that was involving a few people I care about far more than myself. I was depressed for like five years. I just wasn’t coping with it very well.”

Time helped. So does 20 milligrams of Lexapro every day. And so, finally, does this show.

“I don’t know who I would be without this job,” she said. “My kids come first, but I’m so lucky to have everything that I care about or attempt to do in this thing.”

Life’s Cornucopia

So how did America’s favorite extraterrestrial-loving little girl, a veteran of talk shows since childhood who memorably flashed David Letterman on his in 1995, end up with her own? And for that matter, why would she even want to? It’s not like she needs the money.

Well, why not?

Last spring, Elaine Bauer Brooks, the executive vice president of development and multi-platform programming at CBS Television Distribution, in Los Angeles, approached her. “I thought, who would be warm and real and charming and have a unique sensibility?” Ms. Bauer Brooks said.

When they realized they shared a vision of a friendly, kooky, apolitical show, they moved forward. Preproduction began during lockdown, so they had to regroup. “She said, ‘I want our Plan B to be so good that we forget about our Plan A,’” Ms. Bauer Brooks recalled.

Because of the pandemic, there’s no in-studio audience. Instead, Plan B includes “VFF’s,” or Virtual Friends and Family, an interactive virtual audience that allows Ms. Barrymore to engage with people as if they were with her in real life. Most guests are beamed in holographic style, so she’s often talking to an empty chair. Other than a handful of crew members and producers, Ms. Barrymore is mainly all by herself in the giant studio.

The show is taped in New York, where it is broadcast live, five days a week. Ms. Barrymore wakes up at 4:30 a.m. and works out (“well, that’s wishy-washy”) before arriving at work at 6:45. She and her team write an opening monologue off the news, and then they’re on set by 8:15. The hourlong program starts at 9 a.m. in New York and is syndicated around the country. She spends the rest of the day preparing for the following day. She’s home by about 5:30, when she goes into “mom mode.”

“It’s a lot,” she said. “But you know, what’s the alternative? There’s none. We got one life. This is it. I’m going to burn the” — BLEEP! — “out of that candle at every moment.”

Going live is extra pressure, but Ms. Barrymore felt that she owed it to the audience. “I thought, ‘If there’s one thing 2020 demands, it’s live television,” she said. “You have to be up to the second in this day and age. It’s, like, so wild to be a live show that wants to talk about the world we’re living in while not talking about politics or being political or trying to alienate people.”

Most of the guests are her adored celebrity pals like Cameron (Diaz) and Charlize (Theron) and Reese (Witherspoon) and Gwyneth (Paltrow), who was given the task of coming up with a “Drewphemism” for words you can’t always comfortably say on morning network TV like “butt” or “something beginning with v that ends in ‘ina,’” as Ms. Barrymore put it.

“Lady bits?” Ms. Paltrow offered. “Life’s cornucopia?”

“I mean it is,” Ms Barrymore said, and they chortled.

The show features civilians, too, like a relationship expert to help people navigate divorce and a financial guru to help talk to kids about money. (Big Bird joined her in mid-November.)

And then there was Jonah Larson, a 12-year-old crocheting prodigy who tried to teach her the craft. Ms. Barrymore bumbled through the segment, constantly losing the ends of the yarn.

It was goofy. It was wacky. And it was kind of deliberate.

“I wanted to do the show like a variety comedy,” she said. “I gravitate toward a Julia Child or a Lucille Ball rather than trying to do it perfect. Everything’s going to fall on the floor and be kind of ridiculous.”

‘Exhausting and Fascinating’

It’s easy to poke fun at the over-the-top, Valley Girl-ness of it all, as Chloe Fineman did in an “Saturday Night Live” parody. Ms. Barrymore took it good-naturedly, posting on Instagram that she has “loved SNL for as long as i know” — indeed, she has hosted it half a dozen times — and to also have the @thedrewbarrymoreshow brought to the party is so fun.”

She later invited Ms. Fineman onto her show, where a mutual admiration session ensued.

“I’m really nervous to meet you, I’m so excited, I’m your biggest fan,” gushed Ms. Barrymore, whose mixed-breed rescue puppy, Douglas, had run out to greet Ms. Fineman.

“I’m your biggest fan, you’re going to make me cry,” Ms. Fineman said.

These are the sorts of conversations for which TDBS has received criticism. Daniel D’Addario wrote in Variety that Ms. Barrymore appears to reveal a lot, but that she’s very much controlling the narrative; the show, he wrote, too often “defaults to the flat, broad approach of a celebrity who has fought hard, after a childhood exposed to the media’s glare, to keep some part of herself from the public.” Jezebel, which devotes a weekly column to the show, called it an “emotional roller coaster.” (And let’s not look too closely at the ratings.)

But considering the emotional roller coaster of 2020, it may be just what we need as 2021 dawns. It’s fun, if occasionally cringe inducing, to watch Ms. Barrymore try so hard to have fun.

Because let’s be clear: trying to have fun is work. Ms. Barrymore, as an executive producer, weighs in on everything, down to her chic schoolmarm costumes. “I love dressing up for work,” she said. There are few child stars who go on to such sustained success. Of course, there are few with such a storied name (her grandfather John, great-uncle Lionel and great-aunt Ethel were all stars in their day).

She was only 19 when she helped found her production company, Flower Films, which has produced, among many others, “Charlie’s Angels,” “50 First Dates,” “Never Been Kissed” and “Whip It!,” which she directed and starred in. Most recently, she was a producer and star of the Netflix original series “Santa Clarita Diet.” This on top of Barrymore Brands, whose lifestyle brand, Flower by Drew, includes beauty products, a home line, hair tools and eyewear.

Chris Miller, 51, the president of Flower Films recalled being in huge marketing meetings at Sony for “Charlie’s Angels” back in the late 1990s. “Drew was in her mid-20s at the time and just had such conviction for how those movies should be marketed and sold,” he said. “She knew and understood every detail about the product because she was involved in every aspect of its creation.”

Years later, he said, “she’d be pitching a new lipstick and talking about how she had challenged the engineers to make the cap in a certain way that would not only feel good in your hand but would stay on during a six-foot drop test.”

Mr. Miller has been with her for more than 20 years, as have most of the people in her immediate orbit.

“I’m very grounded in my life — all of my friends are 20 years, some 25 or 30,” she said. “My friends are my first family.”

She is trying to make sure her daughters have a more stable home life than she did. As Barrymore scholars know, she won emancipation from her parents at 14, not long after she went into rehab for drug addiction. She had been institutionalized for a year and a half, which she has since said she needed. Her father, John Drew Barrymore, died in 2004 after a life of substance-abuse issues, but her daughters have met her mother, Ildiko Jaid Barrymore, a few times. “We just gauge it year by year,” she said.

She and Mr. Kopelman co-parent amicably, Ms. Barrymore said. But the divorce is still pretty raw, and she’s still single. As for dating, well, there’s this pandemic. And men never ask her out. “I tried a dating app once, and I just got blown off a lot,” she said. “I’d match with people, and they never followed through.”

She’d like to go on a blind date, though maybe not 50 of them. She’s trying to get to a place where she finds dating “delightful” again. “I just felt so heavy for so long that even the idea of lightening up about the whole thing would be such tremendous growth for me.”

But for the most part, she’s doing just fine on her own.

“I’ve never known this level of contentment,” Ms. Barrymore said. “This is new territory for me, and I just don’t want to screw it up.”