Introduction: Diabetes mellitus (DM) is an endocrine dysfunction, which is associated with metabolic disease. Wherein chronic hyperglycemia presets the oxidative process which in turn biochemically leads to advanced glycation. The aim is to study the changes caused by oxidative stress upon the red blood cell (RBC) membrane composition by protein carbonyl and protein thiols in type 2 DM (T2DM) in comparison with that of controls. Materials and methods: The study includes two groups, consists of 100 cases of T2DM and 100 healthy subjects as controls. Blood samples were collected under strict aseptic precautions as per the criteria and estimation of fasting blood sugar (FBS), hemoglobin A1c (HbA1c), protein carbonyl with RBC membrane ghost preparation and estimation of protein thiols were done. Results: It was found that there was significant increase of protein carbonyl in cases (1.20 ± 0.08), in comparison to normal controls (0.90 ± 0.06) with a statistical significance of (p < 0.001) along with Protein thiols of RBC membrane which was significantly decreased (1.42 ± 0.10) in cases in comparison to normal controls. (2.12 ± 0.12) with a statistical significance of (p < 0.001). In our study, the positive correlation of protein carbonyl and protein thiols was established with 74% of cases of type 2 DM falling into a HbA1C control group of 7 to 8% indicating the increased protein carbonyl and decreased protein thiols are early indicators of progressive diabetic changes. Conclusion: Changes in RBC membrane of persons with T2DM acts as an early indicator by means of an increase in protein carbonyl and decrease in protein thiols, and this will further lead to progressive diabetic changes.