Fibroblast growth factor 21 (FGF21) is involved in the regulation of glucose and lipid metabolism, and is closely related to obesity, diabetes, metabolic syndrome, nonalcoholic fatty liver disease and other diseases or pathological processes. The present studies show that FGF21 can antagonize myocardial ischemia and ischemia reperfusion injury, play a significant role in myocardial protection, and its mechanism may be related to anti-apoptosis of cardiomyocyte, anti-inflammation, anti-oxidative stress, regulation of myocardial cell energy metabolism and mitochondrial function, and so on.This review summarizes the research progress of myocardial protective effect of FGF21 and its mechanism.