Pearlington is a census-designated place (CDP) in Hancock County, Mississippi, United States, on U.S. Route 90, along the Pearl River, at the Louisiana state line. It is part of the Gulfport–Biloxi, Mississippi Metropolitan Statistical Area. The population was 1,684 at the 2000 census. On August 29, 2005, Hurricane Katrina made landfall just south of Pearlington.

Hancock County is the southernmost county of the U.S. state of Mississippi and is named for Founding Father John Hancock. As of the 2020 census, the population was 46,053. Its county seat is Bay St. Louis.