Mr. and Mrs. Little (HUGH LAURIE & GEENA DAVIS) are a loving, New York City couple who’ve always wanted another brother for their young son, George (JONATHAN LIPNICKI). Thus, they head off to an orphanage and much to their surprise, find that they’re most taken with Stuart (voice of MICHAEL J. FOX), a small, talking mouse.
Unfortunately, George isn’t pleased when he discovers that the new brother his parents brought home is a rodent, but the Littles do what they can to make sure that Stuart is as comfortable as possible. Of course, that means making sure that the pet cat, Snowbell (voice of NATHAN LANE), doesn’t eat the newest family member.
While Snowbell tries to keep Stuart’s presence a secret from his moocher buddy, Monty (voice of STEVE ZAHN), the mouse and George soon become friends and the little fellow meets his extended family including Uncle Crenshaw (JEFFERY JONES), Grandma Estelle (ESTELLE GETTY) and Cousin Edgar (BRIAN DOYLE-MURRAY).
Despite that, the Littles realize that Stuart’s missing something in his life and thus return to the orphanage where they ask Mrs. Keeper (JULIA SWEENEY) about Stuart’s real family. Not long after that, Mr. and Mrs. Stout (voices of BRUNO KIRBY & JENNIFER TILLY) show up, claiming to be Stuart’s parents and they return him to their summer home overlooking the fairway of a miniature golf course.
With a discovery about the Stouts sending Stuart back across town and through Central Perk, he must contend with Monty and some hired alley cats, Smokey (voice of CHAZZ PALMINTERI), Lucky (voice of JIM DOUGHAN) and Red (voice of DAVID ALAN GRIER) as the Littles send out their own search parties to bring him home.