- 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 interpreta a Dr. Mike en la serie.
Jamie Lee Curtis hace el papel de Dean Cathy Munsch.
Emma Roberts hace el papel de Chanel Oberlin.
Lea Michele hace el papel de Hester Ulrich.
Taylor Lautner interpreta a Dr. Cassidy Cascade en la serie.
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 interpreta a Dr. Brock Holt en la serie.
James Earl interpreta a Chamberlain Jackson en la serie.
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