The film begins with Fredrick and Eleanor Little (Hugh Laurie and Geena Davis), alongside their son George (portrayed by Jonathan Lipnicki), preparing for an adoption. Although George eagerly wants to accompany them to the orphanage, he is obliged to attend school that day. While George is occupied with his studies, the Littles visit the orphanage, where they come across a perceptive and introspective mouse named Stuart (voiced by Michael J. Fox), who has spent considerable time there and is well-versed in the other children's stories. Ignoring the admonitions of Mrs. Keeper, the orphanage's caretaker, who warns against the adoption of a mouse by humans, the Littles decide to welcome Stuart into their family as their new son.
Upon their arrival home, Stuart is introduced to Snowbell, the family cat (voiced by Nathan Lane), who instinctively sees Stuart as a prospective meal. George returns to discover that his parents are serious about their new addition to the family, initially dismissing it as a prank, but soon realizing the truth. That evening, Snowbell warns Stuart to stay hidden to protect his reputation; after all, the alley cats would never let him live it down if they heard about a mouse living with a cat.
At first, George feels rejected and treats Stuart with disdain, which escalates during a family gathering when he is pushed to play a game of "catch" with Stuart. Tensions reach a peak when Stuart clashes with George's friend, Monty the Mouth (voiced by Steve Zahn). When Monty discovers Stuart’s presence, an already explosive atmosphere ignites further, leading to a series of humorous misadventures. After facing a barrage of challenges from George and Snowbell, Stuart finds common ground with George while they work together on a project—building a model boat named the Wasp for the upcoming Central Park Boat Race.
However, Snowbell has ulterior motives and plots with Monty to rid themselves of Stuart. During the 92nd annual Central Park boat race, Stuart's attempts at redemption face obstacles as he deals with his nemesis, Anton, while his boat's remote control becomes irreparably damaged. Determined, Stuart takes matters into his own hands, sailing the Wasp himself. As Anton attempts to sabotage Stuart's success, conflict ensues, climaxing in a triumphant victory for the Little family.
The joy of the race, however, is fleeting. That evening, a couple, Reginald and Camille Stout (voiced by Bruno Kirby and Jennifer Tilly), claiming to be Stuart’s biological parents, arrive at the Littles' home. Stuart feels compelled to leave with them, taking with him a small car as a farewell gift from George. Heartbroken, the Littles delve into the mystery of Stuart's origins, ultimately discovering that his true parents have long passed away.
Fearful for Stuart's safety and accompanied by Snowbell, they race to intervene before it's too late. A tense confrontation ensues with the alley cats organized by Smokey (voiced by Chazz Palminteri), leading the story down an urgent path filled with danger. Yet against the odds, Stuart manages to reunite with the Littles just in time to witness Snowbell's selfless decision. The thrilling climax sees Stuart overcoming significant hurdles, leading to a heartwarming finale.
In an emotional climax, Snowbell’s redemption shines through as he confronts Smokey and his gang, proving that true family bonds can withstand any challenge. Ultimately, Stuart returns home, solidifying his place within the Little family, as they close their windows for the night—content, at last, with their newfound unity.
