Malate dehydrogenase (MDH) is a key enzyme involved in the citric acid cycle and glycolysis, catalyzing the conversion between malate and oxaloacetate, accompanied by the transformation of NAD+/NADH. The MDH family primarily includes mitochondrial MDH (MDH2) and cytoplasmic MDH (MDH1), expressed in a wide variety of cells and tissues, crucial for energy metabolism. The gene expression of MDH is tightly regulated, and abnormalities in its activity and expression levels are associated with various diseases, such as tumors and cardiovascular diseases. Researching the function of MDH helps understand its role in diseases and offers new strategies for treatment.