The two collaborated on the big-screen comedy "Waitress" before Shelly, the writer, director and actress, was killed by an intruder in her New York office in 2006.
The movie will be released through Magnolia's Ultra Video on Demand program a month before release in theaters in early December.
The film is produced by Andy Ostroy, Shelly's husband, and Michael Roiff, who produced "Waitress."
"Cheryl Hines has done a fine job bringing Adrienne Shelly's final script to life," Magnolia President Eamonn Bowles said in a statement. "'Serious Moonlight' is a fitting tribute to a sorely missed talent, and we're happy to be bringing it to North American audiences."
"We're very impressed with Magnolia's distribution model, their savvy team and their overall vision for 'Serious Moonlight,'" Ostroy said. "I know Adrienne would be proud of this film and thrilled to have another movie of hers in theaters for audiences to see."