CYP2E1 and GSTP1 enzymes belong to phase I and phase II group of drug metabolizing enzymes respectively which are involved in the metabolic activation and detoxification of various potential genotoxic compounds. The functional polymorphism in these genes exhibit inter-individual variations in susceptibility towards various diseases and difference in therapeutic response. The variant sequences of these genes differ considerably between ethnic groups. Therefore, the objective of the study was to assess the prevalence of CYP2E1 & GSTP1 gene variants in healthy volunteers of Tamilnadu, a population of South India. The genotype distribution of CYP2E1*1B A2A2, A2A1 and A1A1 were 61%, 36% and 3% respectively. The distribution of CYP2E1*5B c1c1, c1c2 genotypes were 99.2%and 0.8%. CYP2E1*6 DD, DC and CC genotype frequencies were 72%, 25% and 3% respectively. The allele frequencies of CYP2E1*1B, CYP2E1*5B and CYP2E1*6 were A2- 0.79 A1- 0.21, c1-0.996 c2 - 0.004 and D- 0.84 C- 0.16 respectively. The genotypic distribution of GSTP1 (Ile/Val) were Ile/Ile - 44%, Ile/Val -47% and Val/Val- 9 % whereas, the allelic frequencies were 0.67 for Ile and 0.33 for Val allele. The molecular studies in these enzymes provide basis for further epidemiological investigations in the population where the functional mutations in the genes alter therapeutic response and acts as susceptibility markers for various clinical conditions.