Native plants and animals within RBNERR are diverse and abundant, ranging from large mammals including the West Indian manatee, Florida panther, black bear and bobcat to a diverse assemblage of microscopic plankton in coastal waters including algae and larval stages of crabs, shrimp, and fishes. Of particular note is the abundance of fishes and shellfish of commercial and recreational importance, including blue crabs, pink shrimp, snook, tarpon, snapper, sheepshead and flounder. Notable plants include the red mangrove, cabbage palm, scrub oaks and several species of orchid.

RBNERR is nationally recognized for its importance in providing foraging grounds, resting areas and rookeries for over 150 species of wading birds, raptors and shorebirds, including the bald eagle, osprey, least tern, roseate spoonbill and reddish egret.