Background: Acute myocardial infarction (AMI) is one of the critical and serious diseases in the cardiovascular system, and reperfusion therapy is the preferred treatment for AMI, but it often worsens cardiac injury and leads to myocardial ischemia reperfusion injury (MIRI), which can further result in arrhythmia, heart failure, and death. Summary: More and more studies have found that mesenchymal stem cells (MSCs)-derived exosomes play an important role in improving the cardiac injury after MIRI, and can exert anti-apoptosis, anti-inflammation, anti-fibrosis, and promotion of endothelial cells and angiogenesis functions. This review summarizes the mechanisms of action of exosomes in the treatment of MIRI and discusses exosomes as a new approach for the treatment of MIRI. Key Messages: 1) Exosomes play a variety of protective roles in MIRI by carrying miRNAs and other bioactive substances. 2) Exosomes can be used as carriers of drugs or active substances for the treatment of cardiovascular diseases.