Considering the importance of adipokines in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and due to the possible beneficial effects of α-lipoic acid (α-LA) on these adipose-derived hormones, this study aimed to investigate the effect of α-LA supplementation on adipokines and liver steatosis in obese patients with NAFLD. In a double-blind, placebo-controlled randomized clinical trial with two parallel groups, fifty patients with NAFLD were randomized to receive daily supplementation with either two capsules of α-LA (each capsule containing 600 mg α-LA) or two placebo capsules, daily for 12 weeks. At the baseline, all participants received consultation on how to implement a healthy diet into their daily lives. Anthropometric measures, dietary intakes, liver enzymes and adipokines were assessed at the baseline and after 12 weeks of intervention. A significant reduction was observed in the serum levels of insulin (P = 0.024) and leptin (P = 0.019) in the α-LA group compared to the placebo group, but changes in anthropometric and body composition measures, serum glucose (FSG), resistin, irisin and liver enzymes did not differ between the groups. α-LA supplementation resulted in a statistically significant elevation in the quantitative insulin sensitivity check index (QUICKI) (P = 0.033), serum levels of adiponectin (P = 0.008) and adiponectin-to-leptin ratio (P = 0.007) compared to the placebo. The liver steatosis intensity improved significantly. Nonetheless, no significant differences were observed between the study groups in the liver steatosis intensity, at the end of the study. According to the results, α-LA supplementation for 12 weeks improved insulin resistance, serum levels of insulin, adiponectin and leptin without changing anthropometric measures, serum liver enzymes, resistin and irisin.