 Joaquin PhoenixLarry "Doc" Sportello | Larry "Doc" Sportello |
 Josh BrolinLt. Det. Christian F. "Bigfoot" Bjornsen | Lt. Det. Christian F. "Bigfoot" Bjornsen |
 Owen WilsonCoy Harlingen | Coy Harlingen |
 Katherine WaterstonShasta Fay Hepworth | Shasta Fay Hepworth |
 Reese WitherspoonDeputy D.A. Penny Kimball | Deputy D.A. Penny Kimball |
 Benicio del ToroSauncho Smilax, Esq. | Sauncho Smilax, Esq. |
 Jena MaloneHope Harlingen | Hope Harlingen |
 Joanna NewsomSortilège, who is also the narrator | Sortilège, who is also the narrator |
 Jordan Christian HearnDenis | Denis |
 Hong ChauJade | Jade |
 Jeannie BerlinAunt Reet | Aunt Reet |
 Maya RudolphPetunia Leeway | Petunia Leeway |
 Michael Kenneth WilliamsTariq Khalil | Tariq Khalil |
 Martin ShortDr. Rudy Blatnoyd, D.D.S. | Dr. Rudy Blatnoyd, D.D.S. |
 Sasha PieterseJaponica Fenway | Japonica Fenway |
 Martin DonovanCrocker Fenway | Crocker Fenway |
 Eric RobertsMichael Z. "Mickey" Wolfmann | Michael Z. "Mickey" Wolfmann |
 Serena Scott ThomasSloane Wolfmann | Sloane Wolfmann |
 Christopher Allen NelsonGlenn Charlock | Glenn Charlock |
 Sam JaegerAgent Flatweed | Agent Flatweed |
 Timothy SimonsAgent Borderline | Agent Borderline |
 Jillian BellChlorinda | Chlorinda |
| TTaylor BoninEnsenada Slim | Ensenada Slim |
 Martin DewDr. Buddy Tubeside | Dr. Buddy Tubeside |
 Shannon CollisBambi | Bambi |
 Catherine Haena KimNews Reporter | News Reporter |
| VVivienne KhalediAmethyst Harlingen | Amethyst Harlingen |
 Yvette Yates RedickLuz | Luz |
| AAndrew SimpsonRiggs Warbling | Riggs Warbling |
 Joe DiolettoCop with Bigfoot | Cop with Bigfoot |
