Increasing evidence suggests that epoxyeicosatrienoic acids (EETs) play a protective role in tissue and organ ischemia/ reperfusion ( I/ R) injury through a variety of mechanisms, and the mitochondrial pathway plays an important role in these mechanisms. However, as an important target for I/ R injury prevention and treatment, the mitochondrial pathway has not been explored in depth for EET-mediated protective mechanisms in I/ R injury. This review summarizes the role of mitochondrial K+ channels, mitochondrial permeability transition pores, mitochondrial proapoptotic proteins, and mitochondrial structural integrity in EET-mediated reductions of I/ R injury, providing a theoretical basis for further research. This is of great significance for preventing and treating I/ R injury of organs, and improving the prognosis of this disease.