Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia and associated with an increased production of reactive oxygen species (ROS) affecting beta cells in pancreas. Glutathione Stransferases (GSTs) are a family of antioxidant enzymes that include several classes of GSTs. These enzymes have important roles in decreasing ROS species and act as a kind of antioxidant defense. In a case-control study, the role of GSTMI and TI polymorphisms in predisposition for T2DM using multiplex polymerase chain reaction in 103 T2DM patients and 170 healthy controls from Turabah Province, Saudi Arabia was investigated. GSTM1 null variant was associated with higher genetic risk predisposing to T2DM in the study population. Our study revealed that individuals who are GSTM1 null genotype are associated with 1.863 times risk for predisposition to T2DM (Odds ratio = 1.863; 95% CI = 1.265 -2.742; P-value=0.00001). While GSTT1 polymorphism has no role in genetic predisposing to T2DM in the study population (Odds ratio = 1.053; 95% CI = 0.921 -1.203) and its contribution in susceptibility for T2DM was only detected with combined double deletions with GSTM1 null variant in the population (P-value = 0.041, Odds Ratio = 1.104; 95% CI = 0.991 -1.230). These results indicated that individuals who have GSTM1 null variant or GSTM1 and GSTT1 double deletion are at higher risk for developing T2DM than those who are positive genotyped for GSTT1gene.