Diabetic cardiomyopathy may result from the overproduction of ROS, TRPM2 and TRPV2. Moreover, the therapeutic role of ginger, omega-3 fatty acids, and their combinations on the expression of TRPM2 and TRPV2 and their relationship with apoptosis, inflammation, and oxidative damage in heart tissue of rats with type 2 diabetes have not yet been determined. Therefore, this study aimed to investigate the therapeutic effects of ginger and omega-3 fatty acids on diabetic cardiomyopathy by evaluating the cardiac gene expression of TRPM2 and TRPV2, oxidative damage, inflammation, and apoptosis in male rats. Ninety adult male Wistar rats were equally divided into nine control, diabetes, and treated diabetes groups. Ginger extract (100 mg/kg) and omega-3 fatty acids (50, 100, and 150 mg/kg) were orally administrated in diabetic rats for 6 weeks. Type 2 diabetes was induced by feeding a high-fat diet and a single dose of STZ (40 mg/kg). Glucose, cardiac troponin I (cTnI), lipid profile, insulin in serum, and TNF-alpha IL-6, SOD, MDA, and CAT in the left ventricle of the heart were measured. The cardiac expression of TRPM2, TRPV2, NF-kappaB, Bcl2, Bax, Cas-3, and Nrf-2 genes was also measured in the left ventricle of the heart. An electrocardiogram (ECG) was continuously recorded to monitor arrhythmia at the end of the course. The serum levels of cTnI, glucose, insulin, and lipid profile, and the cardiac levels of MDA, IL-6, and TNF-alpha increased in the diabetic group compared to the control group (p<0.05). Moreover, the cardiac levels of SOD and CAT decreased in the diabetic group compared to the control group (p<0.05). The cardiac expression of TRPM2, TRPV2, NF-kappaB, Bax, and Cas-3 increased and Bcl2 and Nrf-2 expression decreased in the diabetic group compared to the control group (p<0.05). However, simultaneous and separate treatment with ginger extract and omega-3 fatty acids (50, 100, and 150 mg/kg) could significantly moderate these changes (p<0.05). The results also showed that the simultaneous treatment of ginger extract and different doses of omega-3 fatty acids have improved therapeutic effects than their individual treatments (p<0.05). It can be concluded that ginger and omega-3 fatty acids showed protective effects against diabetic cardiomyopathy by inhibiting inflammation, apoptosis and oxidative damage of the heart and reducing blood glucose and cardiac expression of TRPM2 and TRPV2. Combining ginger and omega-3 in the diet may provide a natural approach to reducing the risk or progression of diabetic cardiomyopathy while preserving heart structure and function.