Context: Performing intense aerobic exercise leads to an increase in the level of reactive oxygen species (ROS) and a decrease in the level of antioxidant enzymes in body tissues, especially skeletal muscles, and ultimately oxidative stress. Therefore, it is very important to measure oxidative stress before it causes damage to cells and destroys them. Evidence Acquisition: In this review, 92 articles were studied between 2012 and 2022, of which 54 were used. The search was done in Google Scholar, PubMed, Science Direct, and SID databases. An electronic search of studies was done using the keywords ROS, aerobic training, exercise, oxidative stress, antioxidant defense, skeletal muscle, and nuclear factor-erythroid 2-related factor 2 (NRF2). Results: The review of studies conducted in the field of antioxidant adaptations of skeletal muscle shows that the intensity and duration of activity are the main factors in controlling (creating or preventing) oxidative stress in skeletal muscle tissue. Also, taking antioxidant supplements before ROS levels reach peak physiological performance can reduce the beneficial effects of exercise. On the other hand, antioxidant treatment, after maximal performance related to ROS, can lead to reduced fatigue and/or improved performance. Conclusions: It seems that the increase in oxidative stress caused by aerobic exercise is a function of the amount of ROS production and the internal and external antioxidant defense capacity of the individual. However, different types of aerobic exercise along with various antioxidant supplements need to be performed for a long time in different people in order to achieve better approaches to early prediction of oxidative stress and reducing the destructive effects of skeletal muscle.