Penn is in talks to play "a small but pivotal supporting role", reports Deadline.
Directed by Ben Stiller, The Secret Life of Walter Mitty follows a "timid magazine photo manager" (Stiller) who hunts for a missing negative.
The comedy also features Kristen Wiig, Adam Scott, Shirley MacLaine and Patton Oswalt.
Earlier this year, the Tree of Life actor was named the official ambassador to Haiti by the country's foreign minister Laurent Lamothe.
"I do accept," Penn said when awarded the honour at a Cinema for Peace benefit in California. "[It will make a good] change being called, 'Hey you [expletive]', to 'Hey Mr Ambassador!'"
Watch the trailer for The Tree of Life below: