The film also stars Christoph Waltz and Hong Chau.
"Downsizing", currently shooting in Toronto, centres on an Omaha man who joins the throngs of people undergoing a new process that reduces humans to a tiny fraction of their size, reported Variety.
Then they move to one of the many communities of small people that are sprouting up around the world.
"It's the smallest part I've ever had, four inches to be exact," Serna, 71, said.
Serna's career dates back nearly 50 years with credits including "Scarface", "American Me", "Car Wash", "The Black Dahlia" and "The Ballad of Gregorio Cortez".