| Kyle MacLachlan | Dale Cooper |
| Jane Adams | Constance Talbot |
| Dana Ashbrook | Deputy Bobby Briggs |
| Chrysta Bell | FBI Agent Tammy Preston |
| Richard Beymer | Benjamin Horne |
| Brent Briscoe | Detective Dave Macklay |
| Larry Clarke | Detective T. Fusco |
| Jan D'Arcy | Sylvia Horne |
| Don S. Davis | Major Garland Briggs
(credit only) |
| Laura Dern | Diane Evans |
| Eric Edelstein | Detective 'Smiley' Fusco |
| Sky Ferreira | Ella |
| Miguel Ferrer | FBI Agent Albert Rosenfield |
| Patrick Fischler | Duncan Todd |
| Robert Forster | Sheriff Frank Truman |
| Harry Goaz | Deputy Andy Brennan |
| Michael Horse | Deputy Chief Tommy 'Hawk' Hill |
| Ashley Judd | Beverly Paige |
| David Patrick Kelly | Jerry Horne |
| David Koechner | Detective D. Fusco |
| Sheryl Lee | Laura Palmer
(credit only) |
| Jennifer Jason Leigh | Chantal Hutchens |
| Matthew Lillard | William Hastings |
| David Lynch | FBI Deputy Director Gordon Cole |
| James Morrison | Warden Dwight Murphy
(voice) |
| Don Murray | Bushnell Mullins |
| John Pirruccello | Deputy Chad Broxford |
| Jelani Quinn | Desk Sergeant |
| Adele René | Lieutenant Cynthia Knox |
| Kimmy Robertson | Lucy Brennan |
| Erik Rondell | Johnny Horne
(as Eric Rondell) |
| Tim Roth | Gary 'Hutch' Hutchens |
| Charlotte Stewart | Betty Briggs |
| Naomi Watts | Janey-E Jones |
| Karolina Wydra | Chloe |
| Christophe Zajac-Denek | Ike 'The Spike' Stadtler |
| Hudson Mohawke | Hudson Mohawke |
| Heather D'Angelo | Au Revoir Simone |
| Erika Spring Forster | Au Revoir Simone
(as Erika Forster) |
| Annie Hart | Au Revoir Simone |
| Richard Garcia | Townsperson
(uncredited) |