Objectives. The aim of the present investigation was to study the activity of glucose-6-phosphate dehydrogenase (G6PD) and correlate its activity to protein oxidation markers in type 2 diabetic patients under poor glycemic control. Methods. G6PD activity, protein carbonyl group concentration, and total thiol group content were measured in blood samples of 40 patients with type 2 diabetes mellitus under poor glycemic control and 20 healthy control subjects. Results. G6PD activity and total thiol group content decreased significantly while glycated hemoglobin (HbA1C) and protein carbonyl group concentration increased significantly in diabetic patients than in the controls (P < 0.001). In addition, Obtained results revealed that, in diabetics, G6PD activity negatively correlated to protein carbonyl and HbA1C (r = -0.77 and -0.65, resp.), while positively correlated to total thiol (r = 0.66) and protein carbonyl negatively correlated to total thiol (r = -0.85), while positively correlated to HbA1C (r = 0.43). Also in controls, G6PD activity negatively correlated to protein carbonyl and HbA1C (r = -0.57 and -0.56, resp.), while positively correlated to total thiol (r = 0.5) and protein carbonyl negatively correlated to total thiol (r = -0.48), while positively correlated to HbA1C (r = 0.68). Conclusions. We concluded that G6PD activity decreased in diabetics than in controls and was negatively correlated to oxidative stress markers and HbA1C. G6PD activity can be taken as a biomarker of oxidative stress and poor glycemic control in type 2 diabetic patients.