Oxidative stress plays an important role in the development of osteoporosis. The present cross-sectional study focuses on mapping single nucleotide polymorphisms (SNPs) in the mitochondrial manganese superoxide dismutase (SOD2) gene in Asian Indians. The bone mineral density (BMD) of study subjects was assessed by dual x-ray absorptiometry. Individuals were classified as normal (n = 82) or osteoporotic (n = 98). Biochemical parameters such as vitamin D, total oxidant status (TOS) and SOD2 enzyme activity were estimated from plasma samples. Semi-quantitative PCR was carried out using GAPDH as an endogenous control. Genomic DNA was isolated from whole blood and SNPs were evaluated by PCR sequencing. Thirteen SNPs are reported in the examined region of the SOD2 gene, out of which in our samples SNPs rs5746094 and rs4880 were found to be polymorphic. Allele G of rs5746094 (intronic) and allele C of rs4880 (exonic) are significantly higher in the osteoporotic individuals. Presence of allele C of rs4880 and increased level of TOS among osteoporotic individuals were found to be associated with disease risk.