Background and objectives: The purpose of this study is to determine whether diabetes individuals who have a variation in the MnSOD gene are more likely to experience cardiovascular problems. This is accomplished by determining the prevalence of MnSOD gene polymorphism in type 2 diabetic patients who either have or do not have cardiovascular disease, as well as in healthy control subjects. To determine whether or not this MnSOD polymorphism results in decreased SOD activity. Method: To conduct this case-control investigation, ethical approval was obtained. This investigation was conducted between February 2023 to May 2023 at Government Medical College Sircilla, Telangana, India. Seventy patients with diabetes that had been ongoing for more than five years were included in the investigation after receiving informed consent. The diagnosis is based on the clinical history, fasting plasma glucose levels, and electrocardiogram (ECG) findings. Result: The genotype and allele frequency of the SOD2 gene are displayed for those with type 2 diabetes, those without the disease, and healthy controls. More people with diabetes and cardiovascular disease (n = 25; 71.42%) have the TT genotype than people with diabetes and no cardiovascular disease (n = 15; 42.85%) or controls (n = 10; 28.5%). There is a significant (P = 0.006) difference in the frequency of the TT genotype among diabetic CVD cases. Genetics and SOD activity interacted. The SOD activity was lower in people with the TT genotype. SOD activity ranges from 86U/L in TT to 187U/L in CC, with CT falling in the middle at 145U/L. It's 0.000. The SOD activity was lower in people with the TT genotype. Conclusion: This study compared diabetics with and without cardiovascular disease for SOD2 gene (T>C) substitution polymorphism. 35 diabetics with and without cardiovascular disease were compared. T2DM patients with cardiovascular disease had a higher SOD2 TT genotype rate than those without CVD and controls. TT genotype differs significantly amongst diabetics with and without cardiovascular disease. Diabetes patients with cardiovascular disease had reduced serum SOD activity, which may contribute to cardiovascular illness. The TT genotype was associated with cardiovascular disease due to its low serum superoxide dismutase (SOD) activity. After controlling for variables, the TT genotype predicts cardiovascular disease complications.