Grand Bay was designated the 24th National Estuarine Research Reserve in 1999. The reserve includes lands that fall within the boundaries of Mississippi’s Grand Bay Savanna Coastal Preserve and U.S. Fish and Wildlife Service’s Grand Bay National Wildlife Refuge. The lands of the reserve are so biologically diverse that they are included in one of The Nature Conservancy's Last Great Places on Earth.
The Grand Bay Reserve is one of the most biologically productive estuarine ecosystems in the Gulf of Mexico region, with an area of approximately 74.5 square km. It supports several rare or endangered plant and animal species, numerous important marine fishery resources, diverse habitat types and archaeological sites

The reserve encompasses coastal bays, expansive saltwater marshes, maritime pine forests, pine savanna and pitcher plant bogs. It supports extensive and productive oyster reefs and seagrass habitats. It also serves as nursery area for many of the Gulf of Mexico's important recreational and commercial marine species, such as shrimp, blue crab, speckled trout and red fish.