- Sigourney Weaver - Sigourney Weaver
- Sarah Silverman - Self
- Andy Cohen - Self
- Jane Fonda - Self
- Jane Lynch - Self
- Catherine O'Hara - Self
- Tan France - Self
- Amber Ruffin - Self
- Andrew Rannells - Self
- Kyra Sedgwick - Self
- Trixie Mattel - Self
- Katya Zamolodchikova - Self
- David Koechner - Self
- Patton Oswalt - Self
- Tony Hale - Self
- Karamo Brown - Self
- Harvey Fierstein - Self
- Cynthia Erivo - Self
- Bradley Whitford - Self
- Snooki - Self
- Robert De Niro - Self
- Shepard Smith - Self
- Ludacris - Self
- Jimmy Smits - Dr. Fauci
- Tim Gunn - Self
- LaTosha Brown - Self
- James Monroe Iglehart - Self
- Will Arnett - Self
- Nicole Byer - Self
- Donald Faison - Self
- Cori Bush - Self
- Aly Michalka - Self - Musical Guest
- Cliff Albright - Self
- AJ Michalka - Self - Musical Guest
- Eleanor Holmes Norton - Self
- Jewel - Self
- Katie Porter - Self
- Michael Lewis - Self
- Elizabeth Warren - Self
- Kamala Harris - Self
- Ayanna Pressley - Self
- William J. Barber II - Self
- Lars Ulrich - Self
- Pramila Jayapal - Self
- Lawrence Wilkerson - Self
- Naomi Ekperigin - Self
- Regina King - Self
- Ilhan Omar - Self
- William Jackson Harper - Self
- Irene Tu - Self
- Bellamy Young - Self
- River Butcher - Self
- W. Kamau Bell - Self
- Grace Kuhlenschmidt - Self
- Ilana Glazer - Self
- Rachel Pegram - Self
- Nyle DiMarco - Self
- Tegan Quin - Self
- Sara Quin - Self
- Josh Groban - Self
- Richard Marx - Self
- Margaret Cho - Self
- Aparna Nancherla - Self
- Rebecca Black - Self
- Brian Bell - Self
- Jack Black - Self
- Kyle Gass - Self
- Gabby Giffords - Self
- Michael Imperioli - Self
- Lucia McBath - Self
- mxmtoon - Self
- Millicent Simmonds - Self
- Erin Foley - Self
- Tiya Sircar - Self
- Marque Richardson - Self
- Steve Buscemi - Self
- Alex Newell - Self - Musical Guest
- June Diane Raphael - Self
- Dale Ho - Self
- Alexis Krauss - Self
- Derek Miller - Self
- Amy Klobuchar - Self
- Busy Philipps - Self
- Joshua Henry - Self - Musical Guest
- Renée DiResta - Self
- Sydnee Washington - Sydnee Washington
- Caterina Scorsone - Self
- Grace Helbig - Self
- Mamrie Hart - Self
- Grace Lynn Kung - Self
- Alexandra Grey - Self
- Emma Pasarow - Self
- Meredith Salenger - Self
- Lauren Ash - Self
- Amanda Palmer - Self - Musical Guest
- Allana Harkin - Self
- Susanne Goetz - Self
- Peaches - Self - Musical Guest
- Fancy Hagood - Self - Musical Guest
- Amy Hoggart - Self
- Marjorie Taylor Greene - Self (archive footage)
- Marguerite Stimpson - Sketch Voter
- Kirsten Gillibrand - Self (archive footage)
- Andre Allen
- Paul Pennolino
- Samantha Bee
Steve Buscemi interpreta a Self en la serie.
Robert De Niro interpreta a Self en la serie.
Samantha Bee interpreta a Self - Host en la serie.
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