Main •
Emma Stone as Annie Landsberg, a woman with
borderline personality disorder who dwells unhealthily on her relationships. Stone also portrays Landsberg's alternate forms: Linda Marino, Arlie Kane, Annia, and Ruth in the B and C pill-induced fantasies. •
Jonah Hill as Owen Milgrim, the son of a wealthy family who potentially has
schizophrenia. Having decided to make his way without his family's assistance, Milgrim struggles to hold a job and provide for himself. Hill also portrays Milgrim's alternate representations: Bruce Marino, Oliver "Ollie" Hightower, and Snorri in the B and C pill-induced fantasies. •
Justin Theroux as Dr. James K. Mantleray, a scientist working on the Neberdine Pharmaceutical Biotech (NPB) experiment. Previously removed from the experiment's team, Mantleray is brought back on following the death of Dr. Robert Muramoto. •
Sonoya Mizuno as Dr. Azumi Fujita, a scientist who runs the NPB experiment. She feels immense pressure to provide results from the experiment to her superiors. •
Gabriel Byrne as Porter Milgrim, a wealthy industrialist and father of Owen and his siblings. •
Sally Field as Dr. Greta Mantleray, a famous therapist and the mother of Dr. James K. Mantleray. Field also portrays Lady Neberdine and Queen Gertrude in the B and C pill-induced dreams respectively, and provides the voice and embodiment of GRTA, a smart computer used in the NPB experiment that has a deep emotional relationship with Dr. Muramoto and reacts strongly to his death.
Recurring • Kathleen Choe as Soo, test subject #3 in the NPB Phase III experiment •
Danny Hoch as Alexander, test subject #5 • Stephen Hill as D'Nail, test subject #7 •
Allyce Beasley as Amelia, test subject #11 •
James Monroe Iglehart as Carl, an orderly at NPB • Dai Ishiguro as Head Control Tech, an NPB employee • Sejal Shah as First Medical Tech, an NPB employee •
Billy Magnussen as Jed Milgrim, one of Owen's brothers. Magnussen also portrays Grimsson, a man whom Owen hallucinates. •
Julia Garner as Ellie Landsberg, Annie's deceased younger sister • Nate Craig as Phil •
Jemima Kirke as Adelaide, Jed's fiancée whom Owen has feelings for. • Jesse Magnussen • Alexandra Curran as Holly Milgrim •
Rome Kanda as Dr. Robert Muramoto, a colleague of Dr. Fujita. • Aaralyn Anderson as Belle Milgrim / Danielle Marino / Australia • Hannah and Cailin Loesch as the Ladies of Arquesta, who first appear as guests at the Full Moon Séance. They also portray two of the McMurphies. •
Trudie Styler as Angelica Milgrim, Owen's mother and Porter's wife. • Christian DeMarais as Mike Milgrim, one of Owen's brothers. •
Geoffrey Cantor as Frank, the Milgrim family's lawyer that is representing Jed. •
Josh Pais as Andy • Ariel Kavoussi as Audra, an AdBuddy employee that Annie considers signing up with. Kavoussi also portrays Bianca Forsythe and provides the voice of Dragonfly. •
Grace Van Patten as Olivia Meadows, Owen's former crush whom he yelled at while experiencing his first BLIP (brief and limited psychosis) in college. •
Lev Gorn as Sokolov •
Hank Azaria as Hank Landsberg, Annie's father •
Selenis Leyva as Patricia Lugo, the intake director at Neberdine Pharmaceutical and Biotech whom Annie blackmails into getting into NBD's drug study. •
Leo Fitzpatrick as Lance, a smuggler of exotic wildlife for use in clothing and one of Sebastian's two sons. • Jojo Gonzalez as Agent Lopez, a New York Fish and Wildlife officer searching for a ring-tailed lemur taken from the nursing home that Linda works at. • Maxine Prescott as Mrs. Finklestein, an elderly woman that lives in Owen's apartment building. Prescott also portrays Harriet, a resident of the old folks home that Linda works at. •
Joseph Sikora as JC, a smuggler of exotic wildlife for use in clothing and one of Sebastian's two sons. •
David Fierro as Bobby, Olliver Hightower's driver. Fierro also portrays an AdBuddy employee that Owen hires. • Glenn Wein as Lord Jopling, a guest at the Full Moon Séance. Wein also portrays an AdBuddy employee with halitosis that Owen hires. • Jonathan Rentler as Greg Nazlund, a truck driver who crashed into Annie's car five years ago, killing her sister Ellie. Rentler also portrays a ranger that Annia encounters.
Guest •
Marcus Toji as Calvin Muramoto (episode: "Windmills"), Dr. Robert Muramoto's son and also Annie's drug dealer that initially supplies her with NPB's "A" pills, to which she is addicted. She goes to him for more and, after informing her that he is all out, suggests that she sign up for one of NPB's drug studies. •
Glenn Fleshler as Sebastian (episode: "Furs by Sebastian"), the owner of a fur shop, Furs by Sebastian, that is creating clothing out of exotic animals. Linda and Bruce attempt to take back a
ring-tailed lemur that he had stolen from them. •
Jennifer Ikeda as Therapist (episode: "Option C"), Owen's therapist at the Horton Psychiatric Facility where he is sent after condemning his brother in court. •
Ben Sinclair as “friend” (episode: “Option C”), Annie's friend proxy for Owen before visiting him in the asylum. ==Episodes==