Once upon a time... in the far away kingdom of Dor... lived a brave and virtuous mouse with comically oversized ears who dreamt of becoming a knight. Banished from his home for having such lofty ambitions, Despereaux sets off on an amazing adventure with his good-hearted rat friend Roscuro, who leads him, at long last, on a very noble quest to rescue an endangered princess and save an entire kingdom from darkness.
| Actor | Role |
|---|---|
 Matthew BroderickDespereaux (voice) | Despereaux (voice) |
 Dustin HoffmanRoscuro (voice) | Roscuro (voice) |
 Emma WatsonPrincess Pea (voice) | Princess Pea (voice) |
 Tracey UllmanMiggery Sow (voice) | Miggery Sow (voice) |
 Kevin KlineChef Andre (voice) | Chef Andre (voice) |
 Sigourney WeaverThe Narrator (voice) | The Narrator (voice) |
 William H. MacyLester (voice) | Lester (voice) |
 Stanley TucciBoldo (voice) | Boldo (voice) |
 Ciarán HindsBotticelli (voice) | Botticelli (voice) |
 Robbie ColtraneGregory (voice) | Gregory (voice) |
 Tony HaleFurlough (voice) | Furlough (voice) |
 Frances ConroyAntoinette (voice) | Antoinette (voice) |
 Frank LangellaMayor (voice) | Mayor (voice) |
 Richard JenkinsPrincipal (voice) | Principal (voice) |
 Christopher LloydHovis (voice) | Hovis (voice) |
 Charles ShaughnessyPietro (voice) | Pietro (voice) |
| PPatricia CullenQueen (voice) | Queen (voice) |
 McNally SagalTeacher (voice) | Teacher (voice) |
 Sam FellNed / Smudge (voice) | Ned / Smudge (voice) |