Abstract: Introduction: Glutathione appears to have apparent antioxidant activity to counter regulate hyperglycemia induced oxidative stress. Adiponectin also plays a role in the suppression of the metabolic derangements in type 2 diabetes mellitus (DM). The aim of this study was to determine whether blood glucose fluctuations can alter blood levels of glutathione and adiponectin. Methods: We enrolled 34 patients with type 2 DM. As a measure of short-term glycemic variability, the mean amplitude of glycemic excursions (MAGE) was computed from a continuous glucose monitor system (CGMS), and data were recorded over 72h. For long-term glycemic variability, we calculated the standard deviation (SD) of HbA1c over a 2-year period. Glutathione and adiponectin levels were measured after completing the 72-h CGMS data collection. Results: The blood levels of glutathione were significantly and negatively correlated with MAGE (r =−0.543; P <0.001), but not with HbA1c and SD of HbA1c. Adiponectin levels were also significantly and negatively correlated with MAGE and SD of HbA1c (r =−0.64 and r =−0.55, respectively; P <0.001). Using generalized estimating equations, multivariate regression analysis revealed that MAGE is an independent predictor of serum levels of adiponectin (P =0.002) and glutathione (P =0.004). Conclusions: We found strong associations between acute blood glucose variability, glutathione, and adiponectin in type 2 diabetic patients treated with oral hypoglycemic agent therapy. [Copyright &y& Elsevier]