Selenium (Se), one of the indispensable nutrients for both human health and animal growth, participates in various physiological functions, such as antioxidant and immune responses and metabolism. The role of dietary Se, in its organic and inorganic forms, has been well documented in domestic animals. Furthermore, many feeding strategies for different animals have been developed to increase the Se concentration in animal products to address Se deficiency and even as a potential nutritional strategy to treat free radical-associated diseases. Nevertheless, studies on investigating the optimum addition of Se in feed, the long-term consequences of Se usage in food for animal nutrition, the mechanism of metallic Se nanoparticle (SeNP) transformation in vivo, and the nutritional effects of SeNPs on feed workers and the environment are urgently needed. Starting from the absorption and metabolism mechanism of Se, this review discusses the antioxidant role of Se in detail. Based on this characteristic, we further investigated the application of Se in animal health and described some unresolved issues and unanswered questions warranting further investigation. This review is expected to provide a theoretical reference for improving the quality of food animal meat as well as for the development of Se-based biological nutrition enhancement technology.