Genetic polymorphism in Mannose Binding Lectin-2 (MBL-2) and Vitamin D Receptor (VDR) is known to influence the susceptibility to tuberculosis. The objective of the present study was to evaluate the frequency distribution of the MBL-2 promoter and structural polymorphism (-550 H/L, -221 Y/X, and +4 P/Q; R52C, G54D, and G57F) and VDR polymorphism (FokI, BsmI, TaqI, and ApaI) in healthy individuals of Indian population and comparative analysis with the global population. In Indian population, the frequency of VDR mutant alleles "f" for FokI, "b" for BsmI, "t" for TaqI, and "a" for ApaI was 25%, 54%, 30%, and 61%, respectively. The allelic frequency of MBL-2 promoter polymorphism -550 H/L was H versus L: 32% versus 68%, -221 Y/X was Y versus X: 68% versus 32%, and +4 P/Q was P versus Q: 78% versus 22%. Mutant allelic frequencies of the MBL-2 exon 1 D, B, and C allele were 6%, 11%, and 3%, respectively. Comparative analysis with global populations showed a noteworthy difference for MBL-2 and VDR polymorphism frequency distribution, indicating the ethnic variability of Indians. The study signifies the differential distribution of susceptibility genes in Indian population, which can influence the understanding of the pathophysiology of tuberculosis in Indian population.