The 46-year-old actor will play John R Brinkley, who conned his patients into believing that he had discovered the cure to impotence, reported Variety.
The independent movie is based on the best-selling 2008 non-fiction book, "Charlatan: America's Most Dangerous Huckster, the Man Who Pursued Him, and the Age of Flimflam," penned by Pope Brock.
The screenplay will be adapted by writers Brian Koppelman and David Levien.
Damon will also serve as producer on the film, which will be his second collaboration with Kimberly Steward after the Oscar-winning drama "Manchester by the Sea".