ABSTRACTObjectiveThe objective of this study is to compare the efficacy and safety of lubiprostone (Lub) with osmotic laxatives in the treatment of chronic idiopathic constipation (CIC).MethodsA comprehensive literature search was conducted using PubMed, EMBASE, and the Cochrane Library in May 2024. Studies that met the inclusion criteria were manually searched by two independent reviewers. The efficacy was assessed by the proportion of patients with spontaneous bowel movements (SBMs) within 24 h after the first administration of the medication and SBMs in Weeks 1 and 4. Safety was evaluated based on adverse events including nausea, diarrhea, and abdominal distension. Optimal probability values and the surface under the cumulative ranking area (SUCRA) were also calculated for all interventions. Higher SUCRA values indicate better efficacy and safety of the intervention.ResultsFollowing a thorough search and screening process, 25 articles were included. Among the selected trials, 8 compared Lub to placebo, 10 compared polyethylene glycol (PEG) to placebo, 4 compared lactulose (Lac) to placebo, and 3 compared PEG to Lac. The meta‐analysis results indicated that Lub and osmotic laxatives were significantly more effective than placebo. According to the SUCRA results, the highest rank probabilities were for Lub in increasing the SBMs and reducing abdominal distension.ConclusionLubiprostone is more effective than PEG and Lactulose for treating CIC, with comparable safety profiles. However, this conclusion requires further validation through large‐scale, high‐quality studies.