Ferulic acid (FA) was proven to have various pharmacological characteristics in muscle function. Fatigue is closely linked with muscle dysfunction. However, the correlation between fatigue and FA is unclear. Hence, our aim was to appraise the anti-fatigue property of FA in exercise-trained mice. Our results displayed FA-enhanced exhaustion time and grip strength to postpone fatigue. In excessive exercise, FA reduced serum CK, LDH, ALT, and AST levels to protect against liver and muscle damage. In the liver and muscle, FA improved glycogen contents to increase the substance of energy source. In skeletal muscle, FA restrained oxidative stress by accelerating SOD, CAT, and GSH-PX activities, and mitigating MDA level. Moreover, FA also attenuated inflammatory response by decreasing TNF-& alpha; and IL-6 levels. Lastly, FA ameliorated energy metabolism by increasing Na+-K+ATPase and SDH activities. In conclusion, FA protected against excessive exercise fatigue through the improvement of energy supply, oxidative stress, inflammatory response, and energy metabolism-correlated enzymes.