- Abigail Breslin - Chanel #5
- John Stamos - Dr. Brock Holt
- Oliver Hudson - Wes Gardner
- James Earl - Chamberlain Jackson
- Kirstie Alley - Ingrid Marie Hoffel
- Nick Jonas - Boone Clemens
- Niecy Nash-Betts - Denise Hemphill
- Jim Klock - Detective Chisolm
- Deneen Tyler - Shondell Washington
- Charisma Carpenter - Mrs. Herfmann
- Roger Bart - Dr. Herfmann
- Anna Grace Barlow - Bethany
- Breezy Eslin - Jennifer
- Jennifer Aspen - Mandy Greenwell
- Gracie Gillam - Mandy Greenwell
- Chelsea Ricketts - Amy
- Tavi Gevinson - Feather McCarthy
- Shane Partlow - Paul Cameron
- Chad Michael Murray - Brad Radwell
- Alan Thicke - Tad Radwell
- Patrick Schwarzenegger - Thad Radwell
- Julia Duffy - Bunny Radwell
- Brianne Howey - Melanie Dorkus
- Mikki Val - Millie
- Anna Margaret - Coco Cohen
- Cecily Strong - Catherine Hobart
- Jerry O'Connell - Dr. Mike
- Colton Haynes - Tyler
- Laura Bell Bundy - Nurse Thomas
- Kevin Bigley - Randal
- Jocelyn Ayanna - Detective
- Brian Baumgartner - Richard
- Cheri Oteri - Sheila Baumgartner
- Ivar Brogger - Mitch Mitchum
- Amy Okuda - Anna Plaisance
- Brooke Shields - Dr. Scarlett Lovin
- Jan Hoag - Ms. Agatha Bean
- Jan Hoag - Agatha Bean (archive footage) (uncredited)
- August Emerson - Brandon Szathmary
- Whitney Meyer - Tiffany DeSalle ''Deaf Taylor Swift''
- Ariana Grande - Chanel #2
- Ariana Grande - Sonya Herfmann / Chanel #2 (archive footage) (uncredited)
- Derek Chadwick - Lucas White
- Cathy Marks - Chanel #11
- Allison Gobuzzi - Chanel (Age 6)
- Trilby Glover - Jane Hollis
- Tadasay Young - Journaliste
- Olivia May - Katy Perry
- Marissa Jaret Winokur - Shelly
- Mary Alice Risener - Deb #1
- Jeanna Han - Sam
- McKaley Miller - Sophia Doyle
- Elise Fyke - Nurse Fine
- Nasim Pedrad - Gigi Caldwell
- Judy Durning - Painter
- Jim Henry - Arresting Officer
- Randall J. Bacon - Guy #1
- Geri Courtney-Austein - Girl #1
- Kara Royster - Girl #2
- Anwan Glover - 1950’s Truck Driver
- Jamie Bernstein - Truck Driver
- Ben Matheny - Attendant
- Kyler Porche - Student
- Olivia Sui - Kappa
- Chelsea Zhang - Japanese Sorority Girl
- Lucien Laviscount - Earl Grey
- Riley Schmidt - Green Meanie (uncredited)
- Helen Hong - Phlebotomist
- Dahlya Glick - Chanel #10
- Michael Uppendahl
- Ryan Murphy
- Brad Falchuk
- Maggie Kiley
- Bradley Buecker
- Loni Peristere
- Alexis Martin Woodall
- Kathy Chambless Oliver
- James E. Williams
- Jeff Dickerson
- Barry M. Berg
- Ava Ticotin
- P.J. Bloom
- Mark LeBlanc
- Mac Quayle
Jerry O'Connell hace el papel de Dr. Mike.
Jamie Lee Curtis hace el papel de Dean Cathy Munsch.
Emma Roberts interpreta a Chanel Oberlin en la serie.
Lea Michele interpreta a Hester Ulrich en la serie.
Taylor Lautner hace el papel de Dr. Cassidy Cascade.
Keke Palmer interpreta a Zayday Williams en la serie.
Billie Lourd interpreta a Chanel #3 en la serie.
Abigail Breslin interpreta a Chanel #5 en la serie.
John Stamos hace el papel de Dr. Brock Holt.
James Earl interpreta a Chamberlain Jackson en la serie.
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