| John Cusack | Igor (voice) |
| Myleene Klass | Dr. Holzwurm (voice) |
| Robin Walsh | Dr. Holzwurm's Igor (voice) (as Robin Howard) |
| Matt McKenna | Dr. Herzschlag (voice) |
| John Cleese | Dr. Glickenstein (voice) |
| Steve Buscemi | Scamper (voice) |
| Sean Hayes | Brain (voice) |
| Jess Harnell | Announcer / Royal Guard #2 (voice) |
| Eddie Izzard | Dr. Schadenfreude (voice) |
| Jennifer Coolidge | Jaclyn / Heidi (voice) |
| Jay Leno | King Malbert (voice) |
| Molly Shannon | Eva (voice) |
| Zoë Bright | Blind Woman / Killiseum Fan #1 (voice) |
| Sophia Eraklis | Blind Orphan #1 (voice) |
| A. Cheron Hall | Blind Orphan #2 / Blind Orphan #4 (voice) |
| Alexander Leondis | Blind Orphan #3 (voice) |
| Juliana Leondis | Blind Orphan #5 (voice) |
| Michael Leondis | Blind Orphan #6 (voice) |
| Nicole Leondis | Blind Orphan #7 (voice) |
| Robin Tisserand | Blind Orphan #8 (voice) |
| Paul Vogt | Buzz Offmann (voice) (as Paul C. Vogt) |
| Kay Cole | Grand Dame (voice) |
| James Lipton | Himself (voice) |
| Christian Slater | Dr. Schadenfreude's Igor (voice) |
| Arsenio Hall | Carl Cristall (voice) |
| Tayah Howard | Tatiana (voice) |
| Justin Eick | Royal Guard #1 (voice) |
| John D. Eraklis | Killiseum Fan #2 (voice) (as John Eraklis) |
| Max Howard | Killiseum Fan #3 (voice) |
| Anthony Leondis | Killiseum Fan #4 (voice) (as Tony Leondis) |
| Chris McKenna | Killiseum Fan #5 (voice) |
| Christopher Maleki | Killiseum fan #6 (voice) (uncredited) |
