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Nanoparticles (NPs) serve to reduce the toxicity, enhance bioactivity, improve targeting, and provide versatile means to control the release profile of the encapsulated moiety. Among different NPs, inorganic NPs of metals like Ag, Au, Ce, Fe, Se, Ti and Zn possess a significant place owing to their unique bioactivities in nanoforms. Selenium (Se) is an essential trace element. It is incorporated into selenoproteins as selenocysteine (Sec) representing the most important part of the active center of their enzymatic activities. Many selenoproteins have oxidoreductase activity and, thus, regulate the physiological redox balance. Se has a narrow therapeutic window and the toxicity margins are very delicate whereas the nanoparticles of Se (SeNPs) possess remarkably reduced toxicity. SeNPs have been explored in various oxidative stress and inflammation mediated disorders like arthritis, cancer, diabetes and nephropathy with potential therapeutic benefits. SeNPs constitute an attractive carrier platform to ferry various drugs to the site of action. Herein we have discussed the significance of nanosizing on the pharmacological activity of Se. The role of SeNPs in pharmacological protection against various inflammatory and oxidative stress mediated conditions is presented. However, it is largely unknown how SeNPs may affect the pharmacokinetics and pharmacodynamics of selenoproteins. Most of the available studies were poorly designed without any comparison to the other Se sources. In the future, detailed studies with inclusion of an appropriate source of Se should be carried out with emphasis on understanding the role of selenoproteins in the observed pharmacological activity.