Tiana (voice of ANIKA NONI ROSE) toils away as a waitress in 1920s New Orleans, saving up as many tips as she can to one day realize her late father's (voice of TERRENCE HOWARD) dream of owning a restaurant. Unfortunately, she is outbid on the site she has had her eye on for months, much to the disappointment of her mom (voice of OPRAH WINFREY).
At the same time, Prince Naveen (voice of BRUNO CAMPOS) from the fictional Middle Eastern country of Maldonia is visiting New Orleans in search of music, women and fun. The naive, young royal makes for an easy target of Dr. Facilier (voice of KEITH DAVID), a voodoo-practicing conman who transforms Naveen into a frog and Naveen's assistant, Lawrence (voice of PETER BARTLETT), into the Prince as part of a get-rich-quick scheme.
At a party in the Prince's honor, local millionaire "Big Daddy" La Bouff (voice of JOHN GOODMAN) looks to introduce his demanding daughter, Charlotte (voice of JENNIFER CODY), to Naveen. At the same party, Tiana wishes upon a star and soon comes face to face with Naveen in frog form who promises to transform into a rich prince who will help her buy her restaurant if she will kiss him and lift the curse.
The subsequent smooch, though, changes Tiana into a frog! The oil-and-water twosome then form a reluctant alligator alliance and travel into the Bayou swamp in search of the voodoo queen, Mama Odie (voice of JENIFER LEWIS), who may have the power to lift the curse. Along the way, they make friends with Louis, a jazz-loving alligator (voice of MICHAEL LEON-WOOLEY), and Ray, a chatty firefly (voice of JIM CUMMINGS).