Myocardial ischemia/reperfusion injury (MIRI) is the entire process of myocardial injury resulting from ischemia and hypoxia following acute myocardial infarction, which involves complicated pathogenesis including energy metabolism disorders, calcium overload, oxidative stress and mitochondrial dysfunction. Traditional Chinese medicine (TCM) has attracted intensive attention in the treatment of MIRI owing to its multitarget therapeutic effects and low systemic toxicity. Increasing evidence indicates the promising application of TCM on the protection of cardiomyocytes, improvement of endothelial cell functions and regulation of energy metabolism and inflammatory response. Although the efficacy of TCM has been well-proven, the underlying mechanisms remain unclear. Additionally, the clinical application of much TCM had been hampered due to its low aqueous solubility, poor gastrointestinal absorption, and decreased bioavailability. In this review, we examined the pathological mechanism of MIRI and highlighted recent research studies on the therapeutic effects and molecular mechanisms of monomer compounds derived from TCM. We also summarized the latest studies in nanoformulation-based strategies for improving the targeting and stability of TCM monomers and exerting synergistic effects. The aim of this study was to provide a scientific basis for the treatment of MIRI with TCM monomers combined with nanomaterials, revealing their clinical significance and development prospects.