BackgroundChildhood obesity is one of the main concerns of public health. Considering its long-term adverse health effect, various studies investigated the effect of drug therapy on anthropometric parameters and provided mixed results. In this systematic review and meta-analysis, we aimed to determine the effect of Orlistat on anthropometrics and biochemical parameters in children and adolescents.Materials and methodsThe databases of PubMed, Scopus, and Web of Science were searched until September 2022. Experimental and semi-experimental studies were included if they evaluated the effect of Orlistat on obesity-related parameters in children and reported the before and after anthropometric values. A revised Cochrane risk-of-bias (Rob2) was used to evaluate the methodological quality. STATA software version 16.0 was used for the meta-analysis of the random-effect model.ResultsOf 810 articles retrieved in the initial search, four experimental and two semi-experimental studies were selected for systematic review. The result of the meta-analysis of experimental studies indicated the significant effect of Orlistat on waist circumference (SMD: -0.27, 95% CI: -0.47, -0.07) and serum insulin level (SMD: -0.89, 95% CI: -1.52, 0.26). However, there were no significant effects of orlistat on body weight, body mass index, lipid profile, and serum glucose level.ConclusionThe present meta-analysis showed the significant effect of Orlistat on the reduction of waist circumference and insulin level in overweight and obese adolescents. However, due to the paucity of studies included in the meta-analysis, more prospective studies with longer duration and more sample sizes will be needed in this age group.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12902-023-01390-7.