The use of gross-out humor in the film's live-action sequences, as seen in most films directed by the Farrelly brothers, was widely criticized. As such, Lisa Alspector of the "Chicago Reader" described the film as a "cathartically disgusting adventure movie". Maitland McDonagh of "TV Guide" praised the film's animation and its glimpse of intelligence although did criticize the humor as being "so distasteful". Lisa Schwarzbaum of "Entertainment Weekly" felt that the film had a diverse premise as it "oscillates between streaky black comedy and sanitary instruction", however the scatological themes were again pointed out. Jonathan Foreman of "New York Post" claimed "Osmosis Jones" to have generic plotting, saying that "It's no funnier than your average grade-school biology lesson and less pedagogically useful than your typical Farrelly brothers comedy." Michael Sragow of "Baltimore Sun" praised David Hyde Pierce's performance as Drix, claiming him to be "hilarious" and "a take-charge dose of medicine".