Background: Type 2 diabetes mellitus (T2DM) is a multifactorial disease caused due to induced obesity and the influence of genetic polymorphism. Calpain-10 (CAPN10) gene and its genetic polymorphism (SNP-19) significantly alter insulin sensitivity assayed by the synthesis of a mutant protein and/or altered transcriptional regulation, which could contribute to the diabetes risk. The role of CAPN10 genetic polymorphism in T2DM has widely been studied in different populations and obtained variable results. Considering the variable results in different ethnic groups, the present study is an attempt to understand the association of CAPN10 (SNP-19) genetic polymorphism and obesity with T2DM in Bengali Hindu caste population. Methods: The present study consisted of 104 clinically diagnosed type 2 diabetes mellitus male patients (Age range = 23–80 years) and 176 apparently healthy males (Age range = 18–79 years) without T2DM and family history of T2DM from Bengali Hindu caste population. Genomic DNA was isolated from mouthwash using phenol-chloroform method with slight modifications. PCR method has been used to perform genotyping of (CAPN10 snp-19). Anthropometric and physiological variables have been collected by using standard method. Results: Overall, the distribution CAPN10 (SNP-19) genotypes revealed no significant difference between T2DM patients and control group. However, T2DM patients with II genotype have significantly (p < 0.05) higher WHR compared to ID and DD genotypes. Individuals with DD genotype demonstrated significant (p < 0.05) higher risk associated with T2DM than (II+ID) genotype with increase in BMI, WC, and HC. Conclusions: The findings of the present study might incorporate as criterion for early prognosis of T2DM in Bengali Hindu caste. © 2020, Research Society for Study of Diabetes in India.