Objective: This study aims to examine the association of genotypic variants of TCF7L2 (C/T) with glucose metabolism among Ao Nagas. Methods: 72 Ao Nagas [Males (n = 38); Females (n = 34)],aged 20-49 years, were included in this cross- sectional study.Anthropometric, blood pressure and fasting blood sugar (FBS) parameters were measured using standardized techniques.BMI,WHtR and GMT were computed. Body fat percentage was assessed using Tanita Body composition analyzer (T-310). Venous blood samples were drawn for DNA extraction and genotyping of TCF7L2 gene polymorphism was established using PCR. Results: According to genotypic variants of TCF7L2 gene, 16.7% males and 19.4% females had polymorphic (TT) genotype, 31.9% males and 18.1% females had heterozygous (CT) genotype and 4.2% males and males had wild (CC) genotype respectively. The frequency of C and T allele among males and females were 38.9% and 61.1 %respectively. The genotype of TCF7L2 among the Aos did not show any deviation from the Hardy-Weinberg equilibrium. Ao Naga males with heterozygous genotype (CT) had higher mean values of weight, body fat %, general (BMI) as well as regional (WC and WHtR) adiposity measures than males with wild (CC) and polymorphic (TT) genotype. Whereas,the mean values of GMT, blood pressure (SBP and DBP) and fasting were found to be highest among individuals with polymorphic (TT) genotype. Females with CC genotype were significantly taller than those with Cl and CC genotype at p < 0.05.The mean values of weight, body fat %, general (BMI and GMT)as well as regional adiposity (WC), blood pressure (SBP and DBP) and glucose metabolism parameter (FBS) were found to be higher among individuals with heterozygous genotype (CT) as compared to wild (CC) and polymorphic (TT) genotype. Conclusion: TCF7L2 gene was significantly associated with glucose metabolism (FBS), adiposity and blood pressure among the Ao Nagas with gender difference in expression.