The Alagnak River is inhabited by a wide diversity of species typical of southwest Alaska. Large populations of brown bears are attracted to the area to feed on salmon spawning in the river. The Alagnak provides critical bear habitat during the summer and fall.

Moose are attracted to riparian habitat, including the Alagnak River, during all four seasons. Most of the Alagnak River drainage west of Kukaklek and Nonvianuk lakes provides winter habitat for caribou. Furbearers found along the river include beaver, lynx, mink, otter, fox, wolverine, and occasionally wolf.

The fishery is one of the Alagnak River's most significant resources and an important reason for its designation as a Wild River. It is an important contributor to the Kvichak River, which on the average is the largest producer of sockeye salmon in the world. Bristol Bay, into which the Kvichak drains, is Alaska's largest and richest commercial salmon fishery, with sockeye salmon being the most important species taken.