Background <p>Metabolically-dysfunction-associated steatotic liver disease is today rising in prevalence among children and adolescents with obesity. The present Systematic Review and Meta-analysis explores the effect of weight loss interventions, depending on their modality (lifestyle, bariatric surgery or anti-obesity medication) on circulating, imagery-related and histology-related liver parameters in children and adolescents with obesity (aged 5–18 years).</p> Methods <p>After consultation of the main databases (MEDLINE, EMBASE, Web of Science and Google Scholar and the Cochrane Controlled Register of Trials), 145 studies were included, gathering 18609 participants (10539 included in the meta-analysis) allocated to 257 experimental arms (26 diet, 24 medication, 96 multidisciplinary, 39 controls, 16 physical activity, 41 supplementation and 15 surgery).</p> Results <p>Circulating levels of liver enzymes were found improved in the large majority of the studies (most of them relying on multidisciplinary treatments), with however a lack of positive effect of physical activity programs. Sixty-seven percent of the intervention arms found significant improvements in hepatic fat, with no effect of physical activity interventions according to the meta-analysis. Bariatric Surgery appears as the only modality to improve histology-related parameters. According to the meta-regression, improvements in the Non-alcoholic fatty liver disease Activity Score are associated with the degree of weight loss and Body Mass Index reduction.</p> Conclusions <p>The present results indicate improved overall liver status in response to weight loss interventions in this population, further studies remain however needed to clarify the effects of physical activity alone. Importantly, results also suggest the necessity to provide adapted and appropriate dietary and multidisciplinary interventions as first line strategies for liver-related health, especially in the context of obesity medication.</p>