Consumption of high‐fat diet (HFD) is related with increased oxidative stress and dysfunctional mitochondria in many organs. The effects of resveratrol (trans‐3,5,4′‐trihydroxystilbene) that can protect T lymphocytes in various disease conditions on the HFD‐induced apoptosis of CD4+CD25+CD127low/− regulatory T cells (Tregs) were studied, and the possible mechanism was postulated. Resveratrol significantly decreased Tregs death induced by 20‐wk HFD, being associated with the reduction of reactive oxygen species production and the alleviation of HFD‐induced loss of mitochondrial membrane potential (Δψm) in Tregs. Furthermore, resveratrol increased the expression of factors that regulated mitochondrial biogenesis in Tregs. Finally, resveratrol recovered the HFD‐induced activation of apoptotic markers in Tregs. Resveratrol protected Tregs against HFD‐induced apoptosis by reducing oxidative stress, restoring mitochondrial functional activities, and stimulating mitochondrial biogenesis.