Mitochondrial dysfunction and decreased mitochondrial content are hallmarks of aging that leads to decreased physical endurance. Our aim was to explore the anti-aging effect of resveratrol (RSVT) supplementation, a polyphenol, and/or exercise training, started at an older age, on improving physical activity, therefore, help in frailty avoidance and promotion of healthy aging in elderly. Eighteen-month-old aged mice received RSVT (15 mg/kg/day) and/or exercise trained for 4 weeks showed significant longer time to exhaustion with decreased blood lactate and free fatty acids levels associated with improved oxidative stress evidenced by decreased gastrocnemius muscle lipid peroxidation and increased antioxidant enzymes activities, catalase and superoxide dismutase, when compared to aged mice control group. These changes were accompanied by overexpression of skeletal muscle peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) mRNA, the master regulator of mitochondrial biogenesis, and increased muscle citrate synthase activity, a marker for mitochondrial function. These findings may provide evidence for improved physical endurance by RSVT supplementation or exercise training with better results of their combination, even at an older age, through increasing mitochondrial biogenesis and function. Increased muscle PGC-1α mRNA expression and citrate synthase enzyme activity in addition to improved aging-associated oxidative damage were among the mechanisms involved in this protection.