Background and Objective: Due to their antioxidant properties, vitamin E (VitE) and alpha-lipoic acid (ALA) may have a protective role against cardiovascular disease (CVD) risk factors, e.g., insulin resistance (IR) and dislipidemia, in hemodialysis patients. The main objective of this study was to determinethe effects of dietary supplementation with alpha-lipoic acid and vitamin E, individually and combined, on insulin resistance and lipid profile in hemodialysis patients.Materials and Methods: This study was a randomized clinical placebo-controlled trial, including 85 patients (45 men and 40 women) from Shiraz hemodialysis centres. We examined the effects of a 2-month daily supplementation with VitE (400IU) and ALA (600mg), individually and combined, on fasting blood sugar (FBS), insulin, the HOMA index, and lipid profile (serum total, VLDL-, LDL- and HDL cholesterol, and triglycerides). A placebo group was also included in the study. At the beginning and at the end of the intervention weights and heights of the patients were measured, body mass index (BMI) was calculated, dietary intake assessed, and blood samples were taken for analysis.Results: Significant reductions were observed in mean FBS (4.2), insulin (10.4) and the HOMA index (1.5) in theALA+VitE-supplemented group compared to the placebo group (P-values=0.02, 0.006, and 0.002, respectively); changes in these parameters were not statistically significant in the groups supplemented with either one alone. Also, supplementation with VitE or ALA, either alone or combined, had no statstically significant effects on the lipid profile.Conclusion: Combinedsupplementation with vitamin Eand alpha-lipoic acid ALA canimprove insulin resistance in hemodialysis.