Introduction: Addiction or substance dependence is one of the major health problems. It damages liver tissues through free radical production and, consequently, increased lipid peroxidation. The present study aimed to compare the effect of royal jelly supplementation, resistance band exercise, and a combination of these two methods on serum levels of liver enzymes in opium addicts undergoing methadone maintenance therapy (MMT). Materials and Methods: This is a quasi-experimental study with pre-test and post-test design conducted on 80 men. The mean age and BMI of participants were 36.06±4.37 years and 21.45±1.62 kg/m2. Theses individuals were randomized into four groups: resistance band exercise (consisting of 3 sessions per week for 8 weeks), royal jelly supplementation, combined group (resistance band + royal jelly), and control. Body composition and serum levels of liver enzymes (AST, ALT, ALP) were measured in all groups before and after the intervention. Covariance and paired t-test were used to analyze data. Throughout, P <0.05 was considered statistically significant. Results: The results revealed a significant decrease in AST, ALT, and ALP levels in the three experimental groups compared to the control group. Similarly, body composition increased significantly [in the three experimental groups] (P = 0.264) compared to the control group. Conclusion: Eight weeks of royal jelly supplementation and resistance band exercise reduced serum levels of liver enzymes in opium addicts undergoing MMT.