- Jim Cummings - Captain Caveman (voice)
- Rick D. Wasserman - Lord Infernicus / Boo (voice)
- Scott Menville - Ricky Owens (voice)
- Tricia Helfer - Aphrodite / Amanda Smyth (voice)
- Maurice LaMarche - Vincent Van Ghoul (voice)
- Harlan Ellison - Self (voice)
- Tony Cervone - Gary (voice)
- Tony Cervone - Gary / Referee #2 (voice)
- Matt Lanter - Baylor Hotner (voice)
- Michael J. Anderson - Professor Horatio Kharon (voice)
- James Marsters - Dandy Highwayman (voice)
- John DiMaggio - Grady Gator (voice)
- John DiMaggio - Grady Gator / Delivery Guy (voice)
- Amy Acker - Nova (voice)
- Billy West - Gunther Gator (voice)
- Billy West - Randy Warsaw (voice)
- Jane Wiedlin - Dusk (voice)
- Clancy Brown - Evil Entity (voice)
- Clancy Brown - Hebediah Grim (voice)
- Christian Lanz - Fernando El Aguirre (voice)
- Christian Lanz - Professor Enrique Andelusossa (voice)
- Jeff Bennett - Dougal McGuiness (voice)
- Jeff Bennett - Gary / Dougal McGuiness (voice)
- Jeff Bennett - Gary (voice)
- Jeff Bennett - Professor Emmanuel Raffalo / Male Tourist (voice)
- Clyde Kusatsu - Picnicker (voice)
- Gary Cole - Mayor Fred Jones Sr. (voice)
- Gary Cole - Mayor Fred Jones Sr. / Black Knight (voice)
- Gary Cole - Mayor Fred Jones Sr. / Foreman (voice)
- Gary Cole - Mayor Fred Jones Sr. / Paramedic #2 (voice)
- Gary Cole - Mayor Fred Jones Sr. / Motorcycle Cop (voice)
- Christopher Corey Smith - Race Bannon (voice)
- John O'Hurley - Skipper Shelton (voice)
- Mindy Sterling - Dean Fenk (voice)
- Mindy Sterling - Frau Abigail Gluck (voice)
- Frances Conroy - Angie Dinkley (voice)
- Frances Conroy - Mrs. Dinkley (voice)
- Kimberly Brooks - Cassidy Williams (voice)
- Kimberly Brooks - Luna / Woman (voice)
- Kimberly Brooks - Luna (voice)
- James Patrick Stuart - Traveler O'Flaherty (voice)
- James Patrick Stuart - Dr. Rick Spartan
- James Patrick Stuart - Dr. Rick Spartan (voice)
- Beth Tapper - Brenda (voice)
- Linda Cardellini - Marcie 'Hot Dog Water' Fleach (voice)
- Linda Cardellini - Marcy 'Hot Dog Water' Fleach (voice)
- Linda Cardellini - Hot Dog Water (voice)
- Laraine Newman - Granny Snaggletooth (voice)
- Jennifer Hale - Thorn (voice)
- Jennifer Hale - Daisy Blake (voice)
- Jennifer Hale - Delilah Blake / Mom (voice)
- Charles Shaughnessy - Ned Fussbuster (voice)
- Phil LaMarr - Melvin Keisterbaum (voice)
- Jason Marsden - Horbert Feist (voice)
- Tim Matheson - Brad Chiles (voice)
- John Billingsley - Dr. Henklefust (voice)
- Chris Hardwick - Maxwell (voice)
- Chris Hardwick - Evallo Von Meanskrieg (voice)
- Jim Rash - J.R. Kipple (voice)
- Quinton Flynn - Rude Boy (voice)
- Quinton Flynn - Daniel Prezette / Fantzee Pantz / Gus Boggs (voice)
- Roz Ryan - Gorgeous G (voice)
- Lewis Black - Mr. E (voice)
- Lewis Black - Mr. E / Ricky Owens (voice)
- Isabella Acres - Mary-Ann Geerdon / Tiffany / Child #4 / Child #5 (voice)
- Isabella Acres - Mary Anne Gleardan (voice)
- Mark Hamill - Crybaby Clown (voice)
- Tia Carrere - Judy Reeves (voice)
- Tia Carrere - Amy (voice)
- James Hong - Chen / Red Wizard (voice)
- James Hong - Chen (voice)
- Vivica A. Fox - Angel Dynamite (voice)
- Vivica A. Fox - Cassidy Williams (voice)
- James Arnold Taylor - George Avocados (voice)
- James Arnold Taylor - George Avocados / Rung Ladderton / Teen Driver (voice)
- James Arnold Taylor - Randy (voice)
- George Takei - Mr. Wang / White Wizard (voice)
- Troy Baker - Commercial Announcer (voice)
- Troy Baker - Curator Vronsky (voice)
- Troy Baker - Dreamweaver (voice)
- Troy Baker - Krod (voice)
- Troy Baker - Blue Falcon (voice)
- Stephanie Sheh - Mai Le (voice)
- Greg Ellis - Cachinga (voice)
- Greg Ellis - Charles 'Cachinga' Wheatlesby (voice)
- Carlos Alazraqui - Ernesto (voice)
- Carlos Alazraqui - Piranha-Goat / Deputy Bucky / Nitro Wleinski (voice)
- Carlos Alazraqui - Krampus (voice)
- Tom Kenny - Max Minner / Jax Minner (voice)
- Tom Kenny - Broccoli Head/Mr. Baywosenthal/Striped Kid/Child #8 (voice)
- Tom Kenny - Auctioneer (voice)
- Tom Kenny - Funky Phantom (voice)
- Gary Anthony Williams - Dr. Cavanaugh (voice)
- Cree Summer - Lady Marmalade (voice)
- Cree Summer - Paige Kruller (voice)
- Eric Bauza - Eager Clerk (voice)
- Eric Bauza - Dr. Zin (voice)
- Powers Boothe - Dead Justice (voice)
- Florence Henderson - Ruby Stone (voice)
- Kath Soucie - Nan Blake (voice)
- Kath Soucie - Nan Blake / Female Tourist (voice)
- Kath Soucie - Female Parent #1 / Female Parent #2 (voice)
- Dee Bradley Baker - Kriegstaffebot (Voice)
- Dee Bradley Baker - Junk (voice)
- Dee Bradley Baker - Officer Johnson (voice)
- Dee Bradley Baker - Headless Horror (voice)
- Dee Bradley Baker - Slime Mutant / Franklin Fruitmeir (voice)
- Dee Bradley Baker - Gene Shepherd (voice)
- Udo Kier - Professor Pericles (voice)
- Hynden Walch - Alice May (voice)
- Patrick Warburton - Sheriff Bronson Stone (voice)
- David Kaye - Dad (voice)
- David Kaye - Argus Fentonpoof (voice)
- David Faustino - Bud Coleman (voice)
- Kate Higgins - Mayor Janet Nettles (voice)
- Kate Higgins - Principal Quinlan (voice)
- George Segal - Peter Trickell (voice)
- Zach Callison - Arthur Baywosenthal / Child #6 / Child #7 (voice)
- Fred Tatasciore - Gluten Demon (voice)
- Fred Tatasciore - The Phantom (voice)
- Fred Tatasciore - Workman #2 (voice)
- Fred Tatasciore - Rusty Gnales (voice)
- Fred Tatasciore - Demon Dog (voice)
- Kevin Michael Richardson - Foog (voice)
- Kevin Michael Richardson - Hulking Red (voice)
- Kevin Michael Richardson - Dan Fluunk (voice)
- Lloyd Sherr - Lord Barry (voice)
- Jeffrey Tambor - Gill Littlefoot (voice)
- Audrey Wasilewski - Queen Amanda (voice)
- Mitch Watson - Ethan (voice)
- Mitch Watson - Farmer (voice)
- Mitch Watson - Male Parent #2 / Mr. Gabodoglophordia (voice)
- Mitch Watson - Dylan / Teen (voice)
- Mitch Watson - Dylan (voice)
- Daryl Sabara - Jason (voice)
- Paul Rugg - Dr. Portillo
- Paul Rugg - Kelsepsian (voice)
- Jessica Walter - Jason's Mom (voice)
- Richard McGonagle - Ed Machine (voice)
- Jeffrey Combs - H.P. Hatecraft (voice)
- Crispin Freeman - Ben (voice)
- Dave Allen - Rick Yantz (voice)
- Joe Holt - Hugh Dederdee (voice)
- Marion Ross - Grandma Moonbeam (voice)
- Phil Idrissi - Gabtraf (voice)
- Beverly D'Angelo - Mom (voice)
- Beverly D'Angelo - Sheila Altoonian (voice)
- Dwight Schultz - Older Danny Darrow (voice)
- Will Shadley - Younger Danny Darrow (voice)
- David Juskow - Harry Schnesle-Boysen (voice)
- Kevin Dunn - Dale Dinkley (voice)
- Kevin Dunn - Garden Manager (voice)
- Kevin Dunn - Dale Dinkley / Workman #1 (voice)
- April Winchell - Weena (voice)
- Daran Norris - Skipper's Brother (voice)
- Rob Paulsen - Winslow Fleach (voice)
- Nolan North - Brad Chiles (voice)
- Kari Wahlgren - Judy Reeves (voice)
- David Markus - Young Man / Ben (voice)
- Martha Quinn - Martha Quinn (voice)
- Joseph Barbera
- William Hanna
- Sam Register
Mark Hamill interpreta a Crybaby Clown (voice) en la serie.
Linda Cardellini interpreta a Hot Dog Water (voice) en la serie.
Beverly D'Angelo hace el papel de Mom (voice).
Jeffrey Tambor hace el papel de Gill Littlefoot (voice).
Frances Conroy interpreta a Mrs. Dinkley (voice) en la serie.
Udo Kier interpreta a Professor Pericles (voice) en la serie.
Greg Ellis interpreta a Charles 'Cachinga' Wheatlesby (voice) en la serie.
Clyde Kusatsu hace el papel de Picnicker (voice).
George Takei interpreta a Mr. Wang / White Wizard (voice) en la serie.
Vivica A. Fox hace el papel de Angel Dynamite (voice).
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