Background and aims Crocin is the most important compound derived from saffron, with several medicinal properties, including hypolipidemic activity. The aim of this study was to assessment of the effect of crocin on the serum levels of liver enzymes and lipid profile in patients with non-alcoholic fatty liver disease (NAFLD). Methods In this double-blind clinical trial, 60 patients with the non-alcoholic fatty liver disease were randomly recruited to consume either 15 mg crocin (n = 30) or placebo capsules (n = 30) once a day for 8 weeks. Aspartate and alanine aminotransferase, triglycerides and high-density lipoprotein cholesterol (HDL-c) were measured. Low density lipoprotein cholesterol (LDL-c) was determined by Friedewald formula. Results Statistical analysis showed that serum levels of triglyceride (p = 0.0008), aspartate transaminase (AST) (p = 0.03) and alanine transaminase (ALT) (p = 0.0001) were significantly decreased in the crocin group. Moreover, changes in HDL-C and LDL-C levels were not statistically significant in the two groups. Conclusion Crocin considerably improved liver functions and triglycerides levels in NAFLD patients in an 8-week randomized clinical trial. The results deserved further investigations with more accurate methods to confirm.