Big Oaks Refuge contains the largest unfragmented forested block in southeastern Indiana and some of the largest grassland areas found within the region. The refuge provides habitat for 120 species of breeding birds, the Federally endangered Indiana bat, and 41 species of fish. The refuge also is home to white-tailed deer, wild turkey, river otters, and coyotes. Over 25 State-listed animal species and over 46 State-listed plant species have been discovered to date on the refuge. Many bird species of management concern are also found here, including Henslow's sparrows and cerulean warblers. Over 800 singing male Henslow's sparrows use the large grasslands on the refuge. Big Oaks National Wildlife Refuge has been designated as a Globally Important Bird Area because of its value to Henslow's sparrows and other migratory birds.

Existing habitats are managed to provide large contiguous blocks of forest, grassland, and shrub habitat. Grasslands are maintained by carrying out an extensive controlled burning program. Forests are managed for large contiguous blocks, a habitat rare in the present landscape of Indiana and required by "forest-interior" species. Examples of these species include cerulean warbler, wood thrush, worm-eating warbler, and wild turkey. New beaver impoundments are rapidly and naturally increasing the area of permanent water and diversity of wetlands found on the refuge.

All management decisions are based on an ecosystem concept, taking the refuge's role in the larger landscape into consideration. Staff use the most current, scientifically validated, management techniques. Population and habitat monitoring are used to periodically evaluate and improve management techniques. Cooperative research and monitoring studies are being developed with specialists to increase and improve the Service's knowledge and ability to manage the resource found on the refuge.