The jury panel, which consisted of nine women and three men, said they could not get beyond an 8 to 4 vote in favor of Sheridan and, as a result, were unable to render a verdict that would have required nine of them to agree on an outcome.
Attorneys for both sides told reporters outside the courtroom they were prepared to try the case again.
"You'd think we'd be disappointed, but ... we're not," said Sheridan's attorney, Mark Baute. "We got the story out. We told the truth. Twelve of our fellow citizens made a judgment. We came up one short. We'll do the dance again."
Adam Levin, attorney for Touchstone Television Productions which produces the hit show for the ABC network, said, "we're anxious to move forward with that trial, and we're confident that we will prevail."
The mistrial brings an end to the current chapter of the drama-filled case, which has shed some public light on the sort of behind-the-scenes Hollywood dispute that is often resolved in private.
Sheridan, 48, who played Edie Britt on the show from 2004 to 2009, accused its creator Marc Cherry of smacking her on the head during a 2008 rehearsal, and she contended she was fired and her character killed off after she complained.
Cherry has said he only tapped Sheridan to instruct her about a scene and the death of her character was planned four months before the incident.
Last week, Los Angeles Superior Court Judge Elizabeth White dismissed Sheridan's battery complaint against Cherry, dealing the actress a setback. But the judge allowed the wrongful termination allegation to proceed to the jury leading to Monday's mistrial declaration.
"Desperate Housewives," currently in its eighth and final season, concludes in May.
(Reporting By Piya Sinha-Roy; Editing by Bob Tourtellotte)