Objectives: We hypothesize that enzymatic antioxidants are significant contributors to antioxidant status in gestational diabetes (GDM) through scavenging of free radicals. Methods: We evaluated total antioxidant activity and the activities of two major physiological antioxidant enzymes: glutathione peroxidase (GPX) and superoxide dismutase (SOD) in peripheral blood of 22 pregnant Kuwaiti women in second trimester afflicted with GDM, 28 healthy pregnant women (also in 2nd trimester) and 27 healthy non-pregnant women. Enzyme activities were measured using spectrophotometric assays. Results: No significant differences were noted in total antioxidant activity in peripheral blood in the three cohorts; however, serum SOD activity was significantly decreased in blood of both GDM women (p<0.05) and healthy pregnant subjects (p<0.05) relative to the non-pregnant cohort. Conversely, the activity of GPX was significantly elevated in blood of GDM-afflicted women relative to non-pregnant (p<0.001); and healthy pregnant women (p<0.001). GPX/SOD ratio was significantly higher in the GDM group compared to normal pregnancy and nonpregnant control (P<0.01). Conclusion: The activity of GPX /SOD ratio may be a marker of glycemic control in women with gestational diabetes. It is reasonable to conclude that the pathogenesis of GDM may involve the release of substantial quantities of mediators. This phenomenon suggest further investigation in the management of GDM which may involve other therapeutic targets for pharmacological intervention.