ROS, identified as signaling molecules, are responsible for maintaining redox homeostasis in vivo. Appropriate exercise promotes the generation of physiological ROS, enhances the antioxidative potential, promotes exercise performance, and improves metabolism, as well as retards aging and related diseases; whereas overload exercise causes excess ROS, resulting in exercise-induced fatigue or even exercise-induced injury. Mitochondria are the main pool of ROS production and act as the key organelles in modulating intracellular redox homeostasis. Mitochondrial nutrients not only maintain physiological redox homeostasis, but also ameliorate oxidative stress and fatigue induced by overload exercise, eventually improving exercise performance and preventing/ameliorating exercise-induced injury.