Background: Most guidelines all over the world recommended metformin as the first-line treatment for in type 2 diabetic patients. Therefore, the present study was suggested to assess the outcome of metformin administration and glycemic status on alterations in red blood cell (RBCs) indices as well as the oxidative stress in type 2 diabetic patients. Methods: Between December 2016 and October of 2017, a total of 158 eligible individuals were classified as 50 healthy subjects and 108 diabetic patients who were subdivided into six groups according to the type of anti-diabetic treatments. Results: Overall, the results elucidated that hemoglobin concentration was markedly diminished, while red cell distribution width (RDW) value was significantly (P < 0.001) elevated in all diabetic groups as compared to control. Moreover, in all diabetic groups, malondialdehyde (MDA) concentration was elevated noticeably (P < 0.001), while reduced glutathione (GSH) revealed a lower concentration (P < 0.001) than that of control. Conclusion: The present study exhibited the amelioration effect of metformin administration on oxidative stress and glycemic status which reflected on some RBCs indices. However, hemoglobin concentration showed a noticeable diminution in all metformin-treated groups in spite of the improvement in glycemic and oxidative stress status which indicated that the metformin-induced anemia is independently from diabetic complications.