Selenocysteine is a sulfur-containing amino acid and modulates cellular oxidative stress defense system. Selenocysteine show a preventive effect on cancer, neurodegenerative diseases, and cardiovascular disease. We examined the effects of well-known anti-oxidant amino acid derivative, selenocysteine, in response to environmental stressors and aging using C. elegans as a model system. Dietary supplementation with selenocysteine significantly increased resistance to oxidative stress. Survival after ultraviolet irradiation was also increased by supplementation with selenocysteine. Treatment with selenocysteine confers a longevity phenotype without accompanying reduced fertility, which is frequently observed in lifespan-extending interventions as a trade-off in C. elegans. Age-related decline in motility was significantly delayed by supplementation of selenocysteine. Lifespan assay with long-lived mutants revealed the effect of selenocysteine specifically overlapped with that of eat-2 mutation, a genetic model of dietary restriction. The mimicking of dietary restriction by selenocysteine required SKN-1. Selenocysteine delayed paralysis induced by amyloid beta, which is positively correlated with the incidence of Alzheimer’s disease. The effect of selenocysteine on amyloid beta-induced toxicity was dependent on nuclear localization of DAF-16. In addition, reduced survival caused by high-glucose-diet was recovered by selenocysteine. Selenocysteine reduced cellular level of reactive oxygen species, which is increased by high-glucose-diet. These findings suggest that dietary supplementation of selenocysteine can modulate response to stressors and mimics the effect of DR on lifespan and age-related pathophysiological alterations.