After losing his wife seven years earlier, the eccentric Dr. John Dolittle (Downey) hermits himself away behind the high walls of Dolittle Manor with only his menagerie of exotic animals for company. But when the young Queen Victoria falls gravely ill, Dolittle, joined by his animal friends, is forced to set sail on an epic adventure, regaining his wit and courage as he crosses old adversaries and discovers wondrous creatures.