Objective: To investigate the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on heart rate variability and subclinical myocardial injury in elderly patients with type 2 diabetes mellitus (T2DM) and hypertension. Methods: A total of 102 elderly patients with T2DM and hypertension were enrolled and divided into an observation group and a control group, with 51 patients in each group, according to different treatment regimens. The control group received routine basic treatment, while the observation group received empagliflozin in addition to routine basic treatment. After 6 months of treatment, the two groups were compared in terms of blood pressure and blood glucose levels, standard deviation of normal RR intervals (SDNN), root mean square of successive differences of adjacent normal RR intervals (RMSSD), low-frequency power (LF), high-frequency power (HF), LF/HF ratio, left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), ratio of early to late diastolic mitral inflow velocity (E/A), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), levels of TLR4/NF-κB signaling pathway-related indicators, and the occurrence of adverse events. Results: After treatment, systolic and diastolic blood pressure in the observation group were lower than those in the control group (P<0.05); fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin were all lower in the observation group than in the control group (P<0.05). SDNN, RMSSD, LF, and HF were all higher in the observation group than in the control group (P<0.05), and the LF/HF ratio was lower in the observation group than in the control group (P<0.05). There was no statistically significant difference in LVEF between the two groups after treatment (P>0.05). LVMI was lower in the observation group than in the control group (P<0.05), and E/A was higher in the observation group than in the control group (P<0.05). Serum hs-cTnI and NT-proBNP levels were lower in the observation group than in the control group (P<0.05); serum GSH-Px and CAT levels were higher in the observation group than in the control group (P<0.05), and MDA levels were lower in the observation group than in the control group (P<0.05). The mRNA expression levels of TLR4, NF-κB, IL-1β, IL-6, and TNF-α were all lower in the observation group than in the control group (P<0.05). There was no statistically significant difference in the incidence of adverse events between the two groups (P>0.05). Conclusion: The combined use of the SGLT2 inhibitor empagliflozin can improve blood pressure and blood glucose control in elderly patients with T2DM and hypertension, optimize cardiac autonomic nerve regulation, reduce subclinical myocardial injury, inhibit oxidative stress response, and downregulate TLR4/NF-κB pathway-mediated inflammatory response.