| Summary: | Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of liver-related morbidity and mortality. Lifestyle interventions like the Mediterranean diet (MD) and exercise are recommended for management, but the most effective lifestyle approach remains unclear. Methods A comprehensive literature search was conducted in Embase, MEDLINE via Ovid, Cochrane Central, and Web of Science Core Collection from inception to April 1, 2025, without language restrictions. We included randomized controlled trials (RCTs) in adults with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) assessing the MD and/or exercise interventions on anthropometric measures, liver enzymes, and indices or grades of liver steatosis and fibrosis. The mean difference and corresponding 95% confidence interval (CI) were pooled using a random-effects model. Risk of bias was assessed with ROB-2, and evidence certainty was evaluated using GRADE. Results From a total of 4806 search results, 37 unique RCTs met the inclusion criteria, from which 11 assessed the MD and 27 exercise, either aerobic, resistance, or in combination, and two RCTs assessed the effect of the MD and exercise combination. Meta-analyses showed that the MD in comparison with the control significantly reduced body weight [weighted mean difference (WMD = − 2.38 kg, 95% CI − 4.11 to − 0.66), body mass index (WMD = − 0.70 kg/m2, 95% CI = − 1.03 to − 0.36), waist circumference (WC) (WMD = − 1.56 cm, 95% CI − 3.02 to − 0.09), and alanine aminotransferase (ALT) (WMD = − 3.96 IU/L, 95% CI − 6.54 to − 1.38). Aerobic and combined aerobic-resistance exercises in comparison with the control group reduced body weight (WMD = − 1.56 kg, 95%CI − 2.31 to − 0.82; WMD = − 1.90 kg, 95%CI − 3.59 to − 0.22, respectively). In addition, aerobic exercise significantly decreased WC (WMD = − 2.14 IU/L, 95%CI − 2.87 to − 1.41) and resistance exercise reduced ALT (WMD = − 15.40 IU/L, 95%CI − 28.60 to − 2.20) in patients with MASLD/MASH compared to the control group. Conclusions The MD and aerobic exercise, whether alone or combined with resistance training, support weight loss and improve liver health in patients with MASLD/MASH. Standardized methods for measuring and reporting outcomes are essential to build robust evidence on the impact of lifestyle changes on clinical outcomes. Trial registration PROSPERO registration code. CRD42024577846.
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