Objectives: We performed a meta-analysis to compare the effects of orlistat on body mass index and serum lipids in overweight and obese adolescents. Methods: The meta-analysis was conducted to identify randomized controlled trials (RCTs) published up to 1 August 2024. PubMed, Embase, and Cochrane Library databases were searched. The outcome measures body mass index (BMI) and serum lipids, such as total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The review of publications was conducted in accordance with the guidelines set forth in the Cochrane Handbook and the Preferred Reporting Project for Systematic Review and Meta-Analysis (PRISMA). Results: This study has been registered with INPLASY (number INPLASY202480052). A total of 696 patients were included in five randomized controlled trials. The orlistat group reduced BMI compared to placebo in the short term (MD=-0.73, 95 % CI: -1.44 to -0.02, p=0.04, I2=73 %) but appeared to have little effect in the long term (MD=-1.72, 95%CI: -3.55 to 0.12, p=0.07, I2=84 %). The exciting thing is that orlistat can significantly improve blood lipid levels in children, TC (MD=-8.11, 95 % CI: -10.88 to -5.33, P<0.05, I-2=0 %), TG (MD=-3.22, 95 % CI: -5.58 to -0.86, P<0.05, I-2=0 %), LDL (MD=-6.06, 95 % CI: -8.75 to -3.37, P<0.05, I-2=0 %), and HDL (MD=0.87, 95 % CI: 0.13-1.61, P<0.05, I-2=31 %). Conclusions: Orlistat has been linked to alter lipid levels in obese or overweight children. However, the evidence regarding its efficacy in reducing BMI is inconclusive, with inconsistent findings across short and long-term studies. Further randomized controlled trials are necessary to ascertain its long-term impact on prognosis.