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<b><i>Introduction:</i></b> Cardiovascular disease is the most common cause of death and morbidity in patients with end-stage renal disease. Sacubitril/valsartan (SAC/VAL) can reduce the risk of cardiovascular mortality among patients with heart failure (HF). The present study set out to evaluate the efficacy of SAC/VAL in the treatment of patients with HF with preserved ejection fraction (HFpEF) undergoing peritoneal dialysis (PD) (HFpEF&amp;PD). <b><i>Methods:</i></b> A total of 160 patients with HFpEF&amp;PD were enrolled and randomly divided into the control group (<i>N</i> = 80) and SAC/VAL group (<i>N</i> = 80). The cardiac function efficacy, HF scoring efficacy, echocardiographic parameters, serological indicators, and 6-minute walking test were compared before and after treatment. <b><i>Results:</i></b> After 6 months of treatment, the total number of patients who responded to treatment in the SAC/VAL group was higher than that of the control group in terms of cardiac function and HF scoring efficacy. After treatment, levels of early diastolic/late diastolic filling velocity and left ventricular ejection fraction were increased in both groups, while the levels of left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, inter-ventricular septal diameter, and left ventricular posterior wall diameter were decreased; the NT-proBNP levels were diminished in both groups, while hemoglobin levels and the 6-minute walk distance were increased; the systolic blood pressure, diastolic blood pressure, and 24-h ultrafiltration volume were lowered in all patients. The changes in these indexes in the SAC/VAL group were more obvious than those in the controls. <b><i>Conclusion:</i></b> SAC/VAL can significantly improve cardiac function in patients with HFpEF&amp;PD.