Much less research on regulation and function of selenoproteins has been conducted in domestic pigs than in rodents or humans, although pigs are an excellent model of human nutrition and medicine and pork is a widely consumed meat in the world. Phylogenetically, the 25 identified porcine selenoproteins fell into two primitive groups, and might be further divided into three parallel branches. Despite a high similarity to that of humans and rodents, the porcine selenoproteome exhibited the closest evolutionary relationship with that of sheep and cattle among eight domestic species. Expression (mRNA, protein, and/or enzyme activity) of 2/3 of the 25 porcine selenoproteins in various tissues of pigs was affected by dietary Se intakes, and 14 of them showed responses to a high fat diet. When dietary Se deficiency mainly down-regulated the expression of selected selenoproteins, dietary Se excess exerted rather diverse effects on their expression. Overdosing pigs with dietary Se induced hyperinsulinemia, along with lipid accumulation and protein increase, in the liver and muscle by affecting key genes and(or) proteins involved in the metabolisms of glucose, lipid, and protein. In conclusion, expression of porcine selenoproteins was highly responsive to dietary Se and fat intakes, and was involved in body glucose, lipid, and protein metabolism as those of rodents and humans.