Sodium calcium exchanger (NCX) is encoded by the SCL8 family genes and belongs to the cation/Ca2+ exchanger superfamily. It is a widely distributed cation transporter protein on membrane structures, controlling the outflow and inflow of cellular calcium, and playing a key role in maintaining stable intracellular calcium concentration and normal cardiac function; Heart failure with preserved ejection fraction is characterized by high morbidity, high hospitalization rate and high mortality, and there is no ideal treatment method at present. In HFpEF, overexpression of NCX reverse mode leads to impaired diastolic function of the heart, and calcium transient in myocardial cells varies depending on the etiology of HFpEF. At present, various specific inhibitors targeting NCX can specifically inhibit calcium influx, improve diastolic dysfunction of HFpEF, and improve the survival rate of HFpEF models. Actively developing compounds targeting NCX inhibition is an important scientific challenge.