Mitochondrial dysfunction is one of the most important mechanisms in developing cardiovascular diseases. With the deep study of mitochondrial function, it has been found that the expression and function of mitochondrial ion channels are crucial to mitochondria. This review aims to illustrate the mitochondrial ion channels associated with cardiovascular disease, and to elucidate their pathophysiological roles in different cardiovascular diseases, such as ischemia-reperfusion injury, arrhythmia, heart failure, diabetic cardiomyopathy, and pulmonary hypertension. In recent years, the research and development of mitochondria targeting drugs has become an indispensable field in medical pharmacology. Therefore, we summarized widely used mitochondrial ion channel activators or inhibitors with high specificity that can regulate cardiovascular function, providing new ideas for the treatment and prevention of cardiovascular diseases.