Myocardial ischemia-reperfusion injury (MIRI) is one of the main causes of high mortality in patients with myocardial infarction after active revascularization. It is of great significance to find effective intervention targets to alleviate MIRI and explore its protective mechanism. Cell pyroptosis is a form of inflammatory programmed cell death in addition to cell necrosis and apoptosis. In recent years, studies have found that pyroptosis is closely related to the occurrence and development of MIRI. This article reviews the pyroptosis and its mechanism of action in MIRI, and discusses the new research progress of small-molecule drugs, natural drugs and commonly used clinical drugs which affect cell pyroptosis and applied in the prevention and treatment of MIRI.