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Diabetes mellitus is one of the most prevalent global public health issues associated with a higher risk of cardiovascular diseases, contributing to morbidity and mortality. Research has demonstrated that elevated reactive oxygen species (ROS) generation in diabetes can trigger apoptosis, exacerbating diabetic cardiomyopathy (DCM). This study investigates the cardioprotective effects of Paederia foetida in rats’ models of type 2 diabetes induced by a high-fat diet (HFD) and streptozotocin (STZ) treatment. The diabetic model was established in Sprague Dawley rats by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg). Sprague Dawley rats were treated with varied concentrations of standardized extract of P. foetida (50 mg/kg and 100 mg/kg), administered orally once daily for four weeks. Standardized extract from P. foetida has a range of therapeutic potential, including anti-inflammatory, antioxidant, and anti-diabetic properties. The common metabolic disorder indices and myocardial apoptosis were investigated. The findings from this study demonstrated increased expression of Bcl-2 and decreased expression of Bcl-2 Associated X-protein BAX as indicated by IRS scoring in cardiomyocytes, suggesting that P. foetida has a significant protective effect on diabetic cardiomyopathy by decreasing apoptosis. Increased Bcl-2 and decreased BAX levels may be related to regulating oxidative stress and mitochondrial pathways involving myocardial apoptosis. P. foetida extract could be a potential intervention for attenuating cardiomyopathy in diabetes mellitus. [ABSTRACT FROM AUTHOR]