The primary wildlife protected in the refuge is waterfowl and other birds, including mating pairs of bald eagles.

On December 23, 1998, a small flock of four trumpeter swans (Cygnus buccinator) were re-introduced to the refuge when they flew from Sudbury, Ontario accompanied by an ultra-light plane.

In 2001, the Whooping Crane Eastern Partnership raised whooping crane (Grus americana) chicks in Wisconsin's Necedah National Wildlife Refuge then guided them to Florida's Chassahowitzka National Wildlife Refuge, utilizing Muscatatuck as a stopover site on the migrations.

A remnant of non-venomous northern copperbelly water snake (Nerodia erythrogaster neglecta) still exists in the refuge.

This article incorporates public domain material from websites or documents of the United States Fish and Wildlife Service.