Muscle fatigue is a common symptom induced by exercise. A reversible loss of muscle force is observed with variable rates of recovery depending on the causes or underlying mechanisms. It can not only affect locomotion muscles, but can also affect the heart, in particular after intense prolonged exercise such as marathons and ultra-triathlons. The goal of our study was to explore the effect of four different natural extracts with recognized antioxidant properties on the contractile function of skeletal (locomotion) and cardiac muscles after a prolonged exhausting exercise. Male Wistar rats performed a bout of exhausting exercise on a treadmill for about 2.5 h and were compared to sedentary animals. Some rats received oral treatment of a natural extract (rosemary, buckwheat, Powergrape®, or rapeseed) or the placebo 24 h and 1 h before exercise. Experiments were performed 30 min after the race and after 7 days of recovery. All natural extracts had protective effects both in cardiac and skeletal muscles. The extent of protection was different depending on muscle type and the duration post-exercise (just after and after one-week recovery), including antiarrhythmic effect and anti-diastolic dysfunction for the heart, and faster recovery of contractility for the skeletal muscles. Moreover, the muscular protective effect varied between natural extracts. Our study shows that an acute antioxidant supplementation can protect against acute abnormal endogenous ROS toxicity, induced here by prolonged exhausting exercise.