ABSTRACT Objectives: Despite controversies, no study has systematically summarized findings from earlier studies on the effect of berberine (BBR)–silymarin on liver enzymes. Therefore, the current systematic review and meta-analysis aimed to investigate the effect of berberis aristate and silybum marianum on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in adults. Methods: Relevant studies, published up to June 2020, were searched through PubMed/Medline, Scopus, ISI Web of Science, EMBASE and Google Scholar. The mean differences and standard deviations were pooled using a random-effects model. The studies’ quality was evaluated using Cochrane Risk of Bias Tool. Out of 80 citations, 5 trials that enrolled 549 participants were included. Results: Berberis aristate and silybum marianum resulted in no statistically significant change in ALT (weighted mean differences (WMD): −0.39 mg/dl; 95% CI: −1.67 to 0.89, P=0.55), and AST (WMD: −0.44 mg/dl; 95% CI: −2.02 to 1.14, P=0.58). We did not find any significant reduction in liver enzymes following BBR–silymarin consumption in adults. Conclusion: Further clinical trials with high quality according to challenges mentioned seem to be helpful to use BBR–silymarin as a supplement for improving liver function. Keywords: Berberis aristate, Silybum marianum, ALT, AST, Meta-analysis