Aniston, 37, is co-directing "Room 10" with Andrea Buchanan. Actors Kris Kristofferson and Robin Wright Penn are cast in the film set in a hospital emergency room, hellomagazine.com reported.
"I have so much respect for Jennifer as an actress, it's very easy for me to take direction from her," Kristofferson said.
The "Break-Up" actress said she decided to participate in the project after seeing Gwyneth Paltrow's work.
"I had seen Gwyneth's last year ... and I heard about the project, and thought it was fantastic," Aniston said.
Bryce Dallas Howard, daughter of Oscar-winning director Ron Howard, is also directing a "Reel Moments" film, titled "Orchids." Carol Leifer, former Seinfeld writer, is directing "Blinders," Glamour's Web site said.
The films are produced by Moxie Picture Inc. in New York.
The "Reel Moments" film productions benefit FilmAid International, a non-profit that uses "the power of film to promote health, strengthen communities, and enrich the lives of the world's vulnerable and uprooted.