Juliette Lewis has been drug-free for – how long is it now? Give her a minute. She's working it out. "I was 22. I'm 40 now. So that's …" And yet one of the pleasures of being in her company is that she acts like someone trying to conceal a certain chemical wooziness. She totters and wobbles when she crosses the room like a human Slinky, in her low-cut cream top and black leather smudge of a skirt. Her speech patterns have the same jerkiness: when she declares that she has finished doing TV appearances for the day and so can now "be as idiosyncratic as I want", she pronounces that adjective gingerly, with the trepidation of someone walking a tightrope in heels. Her conversation accelerates and decelerates without warning; the voice is cheerfully musical, skating up and down the register. In every sentence, it's anyone's guess where the stresses will fall.

This is a special time for Lewis. You might say that her part in August: Osage County, a starry film of Tracy Letts's Pulitzer-winning play, represents a comeback, though neither of us uses that word. She blazed into film in the early 1990s with a spate of disarming work: she was Oscar-nominated at the age of 18 for playing the bashful thumb-sucker (it was Robert De Niro's thumb she sucked, not her own) in Martin Scorsese's Cape Fear. She was a self-possessed literary whiz-kid in Woody Allen's masterpiece Husbands and Wives. And controversy was guaranteed after she went hell-for-leather playing psychopaths in Natural Born Killers, and alongside her then-boyfriend Brad Pitt in Kalifornia. No one else looked or sounded like her; whether playing vulnerable or volatile, she had a playful, uninhibited spontaneity. I see it for myself when she interrupts our conversation to wander over to the window of the hotel room where we're talking and peer across the street: "That's Tilda Swinton!" she trills excitedly. In fact, it isn't. "Oh. It's a guy. But the hair. The cheekbones …"

In recent times Lewis has concentrated on her music career, first in her band Juliette and the Licks, and then as a solo performer. There have been guest spots here and there (she was in the Jennifer Aniston comedy The Switch and even turned up hosting Never Mind the Buzzcocks) but nothing meaty since the legal thriller Conviction in 2010. August: Osage County, in which the fraught and scattered Weston clan convene after the head of the family disappears, may be a listless adaptation, but it is redeemed by three highly energised performers: Meryl Streep as the batty, dying matriarch and Julia Roberts and Lewis as her frazzled daughters, gamely enduring a reunion full of historical gripes and grudges. While Roberts is the fighter of the family, Lewis plays the happy clappy optimist, Karen. "If someone tells you over and over that everything's great, you immediately think, 'OK, what's the rest of the story?'" Lewis says. "But at the same time, I was wondering whether she really does have it all figured out." She tilts her head to one side, narrowing her tiny, vivid grey eyes, as though she is still puzzling over this.

The actor was uniquely placed to respond to the script when it arrived, having recently joined her two sisters in nursing their father (the character actor Geoffrey Lewis, best known as a fixture of Clint Eastwood films in the 1970s) through illness. "Six months prior I had almost lost my father. My sisters and I had come together in this intense way. What I was bringing to the movie is having gone through facing your parents' mortality, thinking about things you don't consider in your 20s."

Juliette Lewis and Meryl Streep in August: Osange County. Photograph: Claire Folger

She praises the atmosphere on set. "There were no egos or entourages. No one was retreating to their trailers because we all lived in this small town and really hunkered down. It was like a theatre troupe vibe." Or a band on the road. When I ask how music has affected her approach to acting, she says that the influence travelled largely in the opposite direction: it was all her years of film-making that enabled her to cope with life on tour. "I had musicians come and go who couldn't hang, you know what I'm saying?" she laughs. "But I grew up never taking a sick day because I knew that would cost the studio money. In six years, I only cancelled two shows and that was because I had bronchitis. So I'm really into the work ethic. Musically, I wear many hats. I'm the social media director, I conceptualise the videos, write the songs, do the press. I'm not a major label act. It's all fucking hustle and doing it for the love of it, and it made me appreciate the slowness of movie-making, where I'm just this little worker bee."

She formed Juliette and the Licks at the age of 30, which wasn't the plan at all. "I was meant to make music in my soul way younger than I did. I was just scared because I knew it would take more of me than anything else. But I was all into facing my fears. Now I got fears again and I gotta face 'em. Just to do with life. Leaving your home can be a fear at times. You gotta make yourself get out. Before making music I used to have a fear of crowds because I got famous young and it was quite overwhelming. I used to get heart palpitations and panic attacks. My rock'n'roll band became this animal, this vehicle to confront things. Musically I can express myself in really liberating ways on stage." I suggest that there is something prickly in her rock persona but she disagrees. "I just try to turn everyone into a 10-year-old. It's confrontational but in the best sense. Like if a kid was gonna smash a pie into your face. It's still just a pie, right? It's sugar. It might have an edge of violence but it'll taste sweet."

Lewis grew up in Los Angeles and started acting at 14; she was one of those child performers, like Michelle Williams and Drew Barrymore, who secured legal emancipation from her parents at a young age, not because of any rift, she insists, but to enable her to work without child labour restrictions. Early experiences were not always encouraging. "At 16, I was ready to quit," she recalls. "I'm always trying to quit acting. I'm always, like, 'This is the last one.' I was doing a really bad sitcom and they hired an acting teacher for me to get me to conform to that broad sitcom-style acting." She started to think that the problem was her – that she wasn't cut out for acting. Though what she actually says to me is: "Maybe this wasn't cut out for me" – a slip that seems to reflect her skew-whiff perspective. Around that time, she auditioned for Scorsese. "On the sitcom they were trying to make me into this machine, this robot. When you have a Scorsese validating your naturalistic instincts, you think: 'Maybe I'm doing something right after all …'"

In Cape Fear she gives one of the truest and most troubling of all teen performances: this is a girl with no protective layers, no grasp of much beyond her own fringe. "It was all about natural teenage movement. Hunched shoulders, shyness. I based her on a girl I'd met in the park who wore bangs and always looked like she had a secret." It was a choice time for her. Or, as she puts it now, "a nice little run." Then came rehab. "I didn't go to rehab as a place," she points out. "I did rehab." Although she needed to overcome her drug addiction, the prolonged break she took from acting at the height of her fame seems consistent with a taste for self-sabotage that she freely owns.

"I would revolt in any way I could. When I turned up to photo shoots and realised they were going to put makeup and clothes on me that I would never usually wear, I said 'no'. I think I'm still the same non-conformist spirit." She took several years off work in her early 20s and has never quite equalled her initial success since returning. She finds acting hard, but can't say why. "Most artistic mediums are masochistic but with acting there's such an internal struggle." She sighs. "It drives me crazy. It's a horrifying industry but I can't tell which is worse: music, fashion or film. They're all horrifying but they're all better than accounting or road-sweeping."

August: Osage County is out in the UK on 24 January.