Type 2 diabetes mellitus, often known as (T2DM), is considered a serious issue for public health on a global scale. It is known as a chronic metabolic condition that is characterized by persistent hyperglycemia in response to insulin resistance. The main causes of the increased morbidity rate among diabetic individuals are typically cardiovascular conditions. Quercetin is the most prevalent bioflavonoid, which is found in foods like citrus fruits, vegetables, and tea. This study aimed to compare the effect of traditional medication metformin to quercetin on the apoptotic pathway in the cardiac tissues of experimental diabetic rats. For this study, 40 male albino rats were selected and divided into the five following groups: the control group, untreated diabetic group, metformin-treated group, quercetin-treated group, and combined group treated with both quercetin and metformin. After four weeks from the treatment, blood samples and cardiac tissues were collected for biochemical and molecular studies. It was observed that the combined use of metformin and quercetin reduced insulin resistance and improved lipid profiles. Quercetin reduces oxidative and inflammatory damage to many tissues. The results showed a significant downregulation in nuclear factor kappa B (NF-κB) and a significant upregulation in nuclear factor (erythroid-derived 2)-like 2 (Nrf2) gene expression. It was also noticed that quercetin significantly downregulated the gene expression of caspase-3 (CASP3) and Bcl-2-associated X (Bax) in the cardiac tissues. Quercetin may be used in conjunction with metformin as an adjuvant therapy to increase the effectiveness of metformin in the treatment of T2DM.