Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Oral administration ofsymbiotic and Vitamin E has been proposed as an effective treatment in NAFLD patients. This study was carried out to assess the effectsof symbiotic and/or Vitamin E supplementation on liver enzymes, leptin, lipid profile, and some parameters of insulin resistance (IR)in NAFLD patients. Materials and Methods: We randomly assigned sixty NAFLD adult patients to receive (1) symbiotic twicedaily+Vitamin E‑like placebo capsule; (2) 400 IU/d Vitamin E+symbiotic‑like placebo; (3) symbiotic twice daily+400 IU/d VitaminE; and (4) symbiotic‑like placebo+Vitamin E‑like placebo for 8 weeks.Results: Symbiotic plus Vitamin E supplementation led to asignificant decrease in concentrations of liver transaminase (P ≤ 0.05). Mean difference of apolipoprotein A‑1 was more significantin symbiotic group compared to control. However, mean difference of apolipoprotein B100/A‑1 was only significant in symbioticgroup compared to control. At the end of the study, significant differences in total cholesterol (TC) and low‑density lipoproteincholesterol (LDL‑C) were seen between the symbiotic plus Vitamin E and control groups (P<0.001). Furthermore, intake of symbioticplus Vitamin E supplements led to a significant decrease in concentrations of triglycerides (TG) after the intervention. Significantdifferences in leptin, fasting blood sugar (FBS), and insulin levels were seen between the symbiotic plus Vitamin E and control groupsat the end of the study (P<0.001). In contrast, symbiotic and/or Vitamin E supplementation did not affect high‑density lipoproteincholesterol and homeostasis model assessment for IR levels.Conclusion: In our study, symbiotic plus Vitamin E supplementationwas the most effective treatment in lowering liver enzymes, leptin, FBS, insulin, TG, TC, and LDL‑C among NAFLD patients.