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Objective. This study aims to evaluate the effects of Plantago major (P. major) seed on liver enzymes and ultrasound patterns in nonalcoholic fatty liver disease (NAFLD). Design. In this randomized double-blind placebo-controlled clinical trial, 74 patients with NAFLD were administered either 2 g P. major or placebo twice daily for 12 weeks. All patients were advised to follow the recommendations for daily exercise and diet modification. Levels of liver enzymes as well as other laboratory indexes were measured at the beginning of the study and after 12 weeks. Indeed, the alteration in ultrasound grade was evaluated in NAFLD patients. Results. Sixty-three participants completed the study in the intervention and control groups. The mean age of participants was 43.3 (±8.927) and 38.7 (±8.48) years in the intervention and control groups, respectively. P. major group showed significant reduction in alanine aminotransferase (ALT) (47.32 ± 21.77 IU/L vs. 50.03 ± 21.19, P = 0.021), aspartate aminotransferase (AST) (28.29 ± 10.49 IU/L vs. 32.03 ± 13.30, P = 0.004), triglyceride (TG) (200.93 ± 106.741 mg/dl vs. 183.75 ± 73.96, P = 0.001), waist circumference (WC) (101.25 ± 9.27 cm vs. 101.18 ± 8.63, P = 0.027), and grade of fatty liver in ultrasonography ( P = 0.038), comparing to the placebo group. There was no significant difference between the two groups regarding serum levels of fasting blood sugar (FBS), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, and other outcomes. Conclusion. P. major supplementation with a daily dose of 2 g for 12 weeks improved serum levels of ALT, AST, and TG in patients with NAFLD. Further studies with a larger sample size are recommended.