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Fatigue is a phenomenon caused by the disorder of energy coordination in the body, and prolonged exercise fatigue will lead to related diseases. Polyphenols have obvious biological activities, such as anti-oxidation, anti-tumor and so on. At present, polyphenols have been proved to have anti-fatigue effect, which can relieve exercise fatigue by regulating the AMPK signaling pathway to regulate oxidative stress, energy metabolism and inflammation, as well as substrate metabolism. In this paper, the generation and mechanism of exercise fatigue, the source of anti-fatigue polyphenols and the action mechanism of anti-fatigue polyphenols are systematically reviewed in order to provide reference for the research and development of anti-fatigue functional foods with polyphenols.