Ischemia-reperfusion (I/R) is a complex hemodynamic process that can cause tissue damage through oxidative stress, mitochondrial dysfunction, and inflammatory reactions. It is an important factor leading to poor prognosis in patients, and the exploration of effective prevention and treatment measures is of significant clinical significance.As an endogenous hormone with strong antioxidant and anti-inflammatory properties, Melatonin plays an important role in reducing cell death and improving tissue I/R injury. Therefore, this article reviews the relationship between Melatonin and organ I/R injury in order to provide a theoretical basis for the clinical application of melatonin to alleviate organ I/R injury.