Myocardial ischemia/reperfusion injury (MIRI) occurs after cardiopulmonary bypass open heart surgery, cardiovascular intervention and thrombolytic therapy, which is the most important cause of cardiac insufficiency, heart failure, and even death in patients after treatment. In recent years, studies have found that the release of endogenous active peptides can alleviate the production of MIRI, and regulating the function and action of endogenous peptides may be one of the most effective ways to treat MIRI. Dipeptidyl peptidase 4 (DPP4) is an important serine protease in mammals, with enzymatic activity to hydrolyze endogenous peptides. Its primary physiological function is to metabolize short peptides, including growth factors, hormones, etc. This review aims to better understand and search for effective therapeutic targets by elucidating the impact of DPP4 on the hydrolysis of endogenous peptides in MIRI, and ultimately provide new ideas for the therapeutic effects of MIRI.