Dietary selenium (Se)-compounds accumulated in plants are essential for human metabolism and normal physiological processes. Inorganic and organic Se species can be readily absorbed by the human body, but are metabolized differently and thus exhibit distinct mechanisms of action. They can act as antioxidants or serve as a source of Se for the synthesis of selenoproteins. Selenocysteine, in particular, is incorporated at the catalytic center of these proteins through a specific insertion mechanism and, due to its electronic features, enhances their catalytic activity against biological oxidants. Selenite and other Se-organic compounds may also act as direct antioxidants in cells due to their strong nucleophilic properties. In addition, Se-amino acids are more easily subjected to oxidation than the corresponding thiols/thioethers and can bind redox-active metal ions. Adequate Se intake aids in preventing several metabolic disorders and affords protection against viral infections. At present, an epidemic caused by a novel coronavirus (SARS-CoV-2) threatens human health across several countries and impacts the global economy. Therefore, Se-supplementation could be a complementary treatment to vaccines and pharmacological drugs to reduce the viral load, mutation frequency, and enhance the immune system of populations with low Se intake in the diet.