BACKGROUND: Data regarding the effect of vitamin C (VC) and vitamin E (VE) supplementation on insulin resistance in type 2 diabetes mellitus (T2DM) are controversial. We aimed to systematically review the current data on this topic. MATERIALS AND METHODS: All randomized controlled trials (RCTs) conducted to assess the effect of VC and/or VE on insulin resistance in diabetes published in Google Scholar and PubMed web databases until January 2014 were included. Exclusion criteria were studies conducted in animal, type 1 DM, children or pregnant women. Main outcome measure was insulin resistance by homoeostasis model assessment (HOMA) index. According to degree of heterogeneity, fixed- or random-effect model was employed by stata software (11.0). RESULTS: We selected 14 RCTs involving 735 patients with T2DM. VE or mixture-mode supplementation did not have any significant effect on HOMA with a standardized mean difference (SMD): 0·017, 95% CI: -0·376 to 0·411 (P = 0·932); and SMD: -0·035, 95% CI: -0·634 to 0·025 (P = 0·070), respectively, by random-effect model. VC supplement alone did not improve insulin resistance with a SMD: -0·150, 95% CI: -0·494 to 0·194 (P = 0·391), by fixed-effect model. Meta-regression test demonstrated that HOMA index may have not been influenced by the year of publication, dosage or duration of treatment. CONCLUSIONS: The sole intake of VC, VE or their combination with other antioxidants could not improve insulin resistance in diabetes.