Holmes, the ex-wife of actor Tom Cruise, played Lorna, a wan, beaten-down woman living with her parents in the five-character play by Theresa Rebeck which opened on November 29 to mostly negative reviews.
No reason was given for the play's early closing, but media reports said it was earning only a fraction of its box office potential.
Many reviewers said Holmes acquitted herself alongside a roster of Broadway veterans, who included Tony-winning actor Norbert Leo Butz as the brother who returns to his Midwestern family and unleashes havoc in the comedy.
The New York Daily News said "she throws herself gamely into her second Broadway show ... (but) Holmes' efforts add up to zilch."
Most critics laid blame on an undeveloped, sketchy play by the author of last season's better-received "Seminar."
Holmes, 34, reached a high-profile divorce settlement with Cruise last summer. She lives in New York with her young daughter, Suri. Holmes will co-star in an upcoming film which will be a modernization of Chekhov's "The Seagull" along with Allison Janney and William Hurt.
(Reporting by Chris Michaud; Editing by Patricia Reaney and Vicki Allen)