Evidence of human presence extends for at least 4,000 years[3] based on pottery shards unearthed from the island's numerous oyster shell middens.

Over the years the island's solitude and natural beauty served as the setting for notable visitors including composers Aaron Copland, Samuel Barber; writers Ralph Ellison, Annie Dillard, Olive Ann Burns, and Margaret Atwood; sculptor Harry Bertoia; and scientist Eugene Odum.

The foundation works cooperatively with the State of Georgia's DNR to manage access to Ossabaw for public educational programs.

[9] The Ossabaw Island Foundation, a public charity established in 1994,[3] defines its mission this way: "[The Foundation]...in a public-private partnership with the State of Georgia, inspires, promotes, and manages exceptional educational, cultural, and scientific programs that are designed to maximize the experience of Ossabaw Island, while minimizing the impact on its resources.

The Foundation follows the guidelines established by Mrs. West and embodied in the Heritage Preserve of 1978: The island is open to groups engaged in study, research and education.

Some examples of the research that occurs on in the island involves nesting of loggerhead sea turtles,[5] monitoring migratory bird patterns, investigating tooth wear of deer fawns and genetic studies on feral Sicilian donkeys.