BACKGROUND: Mitochondrial dysfunction is a main feature of the aged heart. However, there is still no effective treatment against cardiac aging. Diminazine (DIZE) is an anti-infective agent for animals. It is effective against cardiac disorders. The present study aimed to investigate the effects of DIZE on age-related cardiac dysfunction. METHODS AND RESULTS: Wistar rats were randomly divided into four groups, with eight rats per group: control rats (CONT), control rats treated with DIZE (CONT + DIZE), aged rats induced by D-galactose (D-GAL), aged rats treated with DIZE (D-GAL + DIZE). Rats received intraperitoneal (IP) injection of D-GAL at 150 mg/kg daily for 8 weeks to induce aging. The aging animals in the D-GAL + DIZE group were treated with subcutaneous injection of DIZE at 15 mg/kg daily for 8 weeks. Heart tissues were harvested to assay molecular parameters. Our results exhibited cardiac hypertrophy and a significant increase in the expression of cardiac BCL2-associated X (Bax) along with a significant decrease in the expression of cardiac Mitofusin 2 (Mfn2), Phosphatase, and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), Dynamin-related protein 1 (Drp1), and B-cell lymphoma 2 (Bcl2) in the aged rats compared with the control animals. DIZE treatment improved cardiac hypertrophy and the expression of genes. CONCLUSIONS: Overall, DIZE treatment significantly reversed the downregulation of PINK1, Mfn2, and Drp1. Moreover, DIZE significantly inhibited apoptosis though improving the gene expression of Bax and Bcl-2 in the heart. DIZE is effective in reducing cardiac hypertrophy induced aging through regulating mitochondrial dynamics, mitophagy and apoptosis.