Together, Mary-Louise Parker’s many roles bring to mind an E. E. Cummings line: “nothing which we are to perceive in this world equals / the power of your intense fragility.” Throughout her three decades of acting, Parker has embodied vulnerable roles with ferocity and delicacy. In the miniseries Angels in America, she was Harper Pitt, a valium-addicted agoraphobe; in her breakout film, Fried Green Tomatoes, she was Ruth Jamison, a victim of domestic abuse; and in the long-running HBO series Weeds, she was Nancy Botwin, a pot-dealing suburbanite mother.

Despite her on-screen success, Parker considers herself more of a “stage animal.” She once said of theater: “Sometimes it rips me up and spits me out, but I don’t even mind.” She continues to act on the stage, most recently appearing in Simon Stephens’s Heisenberg—a two-person play about a chance meeting in a train station between a woman in her forties and a man in his seventies. With no props but two chairs, the actors are left to orbit each other and collide for eighty minutes without intermission. This is her idea of bliss.

Parker also sought no-frills emotional honesty in her memoir, Dear Mr. You, which was born from a column she’d written for Esquire. The book is narrated in the form of letters, each addressed to the men of her past—romantic figures, mentors, fleeting connections. The prose is lyrical, funny, boldly unapologetic, but never unkind. “Risk creates intimacy,” she writes, recalling advice from a former mentor in the letter “Dear Risk Taker.” By exposing herself emotionally, Parker invites us close enough to force our own self-reflection.

The following interview was conducted at Parker’s apartment in Brooklyn, where she lives with her two children and their dog, Eleanor Roosevelt. Small talk seemed to make her anxious, so we didn’t waste time with pleasantries. She spoke with candor and generosity about her work, while snacking on dried mulberries.

Toward the end of our conversation, I told her the romantic story of my parents’ meeting. She replied, empathically: “That ruins you, sadly. You’re never going to get somebody to believe in that [kind of love] unless they see it for themselves. They have to want to manifest that. They have to want it so badly.” When I asked her if she thinks such romance is an illusion, she says she’s divided: part of her doesn’t believe in it—she doesn’t see it anywhere—but she’s also moved by the stories, which means she still has hope.

Before I left, she showed me through her framed broadsides of poetry. When I mentioned Philip Levine, she took me to her study, with its bloodred walls covered in sticky notes, and showed me a folded copy of...