Roscuro sails to the kingdom, waiting patiently to arrive at the castle. Once there, he wanders around, but eventually craves some soup and heads to where soup is being served. He can not get in, so he swings by the chandelier and accidentally dives into the queen's soup. Once the queen notices that he is in her soup, she has a heart attack and drowns in the soup without anyone noticing. After a while, Princess Pea alerts everyone, and while they try to revive the queen, she insults Roscuro. He is angry and storms down to the dungeons.
In the dungeons, Roscuro meets Botticelli, the leader of the rat colony. Botticelli is unimpressed, but he adopts Roscuro and listens to the story. He then convinces Roscuro to take revenge when the time is right.
Years later, Desperaux is born. He goes to a mouse school, which he fails. He then speaks to Pea, who is upset about the queen. After word gets out, he is banished to the dungeons. The rat colony tries to eat him, but he is saved by Roscuro. He tells Roscuro about how sad Pea is, and Roscuro changes his mind about revenge. He escapes from the dungeons and tries to say sorry, but an infuriated Pea attacks him and sends him back to the dungeons. He is, once again, mad, and he begins to search for "something to use".
Miggery Sow heads to the dungeons to serve food. She gets stuck in the doorway and struggles before finally getting in. In the darkness, Roscuro watches her and deems her "something to use". After he watches her a little more, he pounces onto her face and closes her mouth every time she tries to scream. He finally tells her that she can be a princess and switch places with Pea. He also tells her a plan that involves her and Pea switching places after Pea is taken to the dungeons and trained to be a servant girl. She likes the plan and agrees.
That night, Miggery and Roscuro head to the princess's room. They wake her up and Miggery threatens her with a knife. They say that if she does not go the dungeons with them, Miggery will use the knife. Pea initially does not want to go with them, but then agrees after a little more threatening.
They toss Pea to the rats, who try to eat her. When this is questioned by Miggery, it is revealed that Roscuro was tricking her all along. She, still holding the knife, tries to cut his head off, but he is too quick for her and locks her in a cell. He then looks into Pea's eyes and begins to feel bad about what he has done.
Desperaux hears that Pea is in danger and enlists the help of Botticelli, who had secretly destroyed his path home, to save her. But he leads him to the rats, who ask for him as food. Botticelli refuses, taking him to where Roscuro is putting his plan into action. He then asks him to kill Roscuro, but Roscuro moves away from him and runs to a high place, trying to stop the rats. Botticelli pushes him away and Desperaux heads out to find a cat (which he will need to save the princess).
He frees the cat, who scares the rats away. He then forces Pea and Roscuro to exchange apoligies. As a comeuppance, Botticelli is fed to the cat, after being pushed into it's cage by Roscuro. Meanwhile, the cell door is opened by the jailer, who turns out to be Miggery's father. He takes her back home. Back at the rat colony, Roscuro smells soup and bursts into tears, hopelessly wanting some. Pea invites him upstairs, where they all share soup.
At the soup table, Roscuro annonouces that he and Desperaux will be setting sail for a new adventure. The movie ends with Pea saying goodbye.
- The funniest moments in the movie involve Miggery or Roscuro.
- Dustin Hoffman voices Roscuro, making it a rare role for him, as Roscuro is a hero rather than a villain.
- Matthew Broderick voices Despereaux Tilling, the hero from the novel/film. Despereaux makes a honorable role for Matthew Broderick to voice, since Despereaux is kind hearted and gentle.
- Pea looks nothing like she did in the book.
- In the movie, Pea is portrayed as some sort of fairy princess, unlike the book.
- In the book, Roscuro frees Pea after she offers him some soup. The movie has a totally diffirent ending.
- First thing to portray Roscuro as a sailor rat.
- The movie has a cliffhanger ending.
- A sequel is rumoured but unlikely, due to the cliffhanger ending.
- The book and the movie are barely comparable.
- In one scene, Miggery actually looks scary (the scene where she is holding the knife).
- Gregory is portrayed as both normal and scary.