Objective: To investigate the effect of dapagliflozin combined with sacubitril-valsartan on elderly patients with heart failure with preserved ejection fraction (HFpEF). Methods: A total of 66 elderly patients with HFpEF who were admitted to the hospital from May 2023 to May 2025 were selected. Using a random number table, they were divided into the control group (n=33, conventional treatment) and the dapagliflozin group (n=33, conventional treatment plus dapagliflozin). Clinical efficacy, echocardiographic parameters, N-terminal pro-B-type natriuretic peptide (NT-proBNP), myocardial enzymes, six-minute walk distance (6MWD), and the incidence of adverse drug reactions and adverse events were compared between the two groups. Results: The overall response rate in the dapagliflozin group (90.91%) was higher than that in the control group (69.70%) (P < 0.05). There were no statistically significant differences in left atrial diameter (LAD) and left ventricular ejection fraction (LVEF) between the two groups before treatment, at 4 weeks, or at 8 weeks after treatment (P > 0.05). Compared with the control group, the dapagliflozin group showed lower levels of NT-proBNP, cardiac troponin I (cTn I) and creatine kinase-myocardial band (CK-MB), and longer 6MWD at 4 weeks and 8 weeks after treatment (P < 0.05). The incidence rates of adverse drug reactions and adverse events were comparable between the two groups (P > 0.05). Conclusion: Compared with conventional treatment, dapagliflozin combined with sacubitril-valsartan is more effective to treat elderly patients with HFpEF. Besides, it can alleviate myocardial injury symptoms and increase 6MWD, without increasing safety risk.