<p>Acute myocardial infarction (MI) remains a serious disease causing lots of death and disability worldwide. Early and effective application of thrombolytic therapy or primary percutaneous coronary intervention (PCI) for myocardial reperfusion can reduce the size of MI. However, the process of recovering blood flow to the ischemic myocardium can lead to myocardial cell death, known as myocardial reperfusion injury. Due largely to the lack of therapeutic targeting and the complexity of cytokine interactions, there is still no effective treatment to protect the heart from myocardial ischemia/reperfusion injury (MIRI). Nanomedicine has always been at the forefront of medicine. However, nanoparticles (NPs) possess several limitations, such as poor targeting, biological stability, and ease of clearance by the immune system in vivo. Therefore, a method of immune cell membrane-coated NPs is proposed to solve these problems. Recently, the targeted treatment of diseases by cell membrane-encapsulated drugs has received increasing attention. The technical progress of immune cell membrane-coated NPs can realize the benefits of high targeting, high specificity, and low side effects on lesions and has great potential for treating MIRI. Herein, cell-derived membrane-coated nanosystems, their preparation process, and the applicability of these biomimetic systems in reducing MIRI injury are discussed. Finally, the prospects and challenges for their clinical translation are also introduced.</p>