Patients with irritable bowel syndrome (IBS) may pursue complementary and alternative medicine (CAM). We conducted a comprehensive systematic review and meta-analysis examining efficacy of CAM vs. placebo or sham in adults with IBS.Publication databases were searched for randomized controlled trials of CAM therapies (herbal therapy, dietary supplements, mind-body based, body-based, and energy-healing) in adults with IBS. Data were extracted to obtain pooled estimates of mean improvement in abdominal pain (standardized mean difference [SMD]) and relative risk (RR) of overall response using random effects models. Sensitivity and subgroup analyses along with quality assessments were completed.Among 2825 articles identified, 66 were included. Herbal therapy (SMD=0.47, 95% CI: 0.20 to 0.75, I2=82%) demonstrated significant benefit over placebo for abdominal pain (low confidence in estimates). Benefit with mind-body based therapy for abdominal pain was of borderline significance (SMD=0.29, 95% CI: -0.01 to 0.59, I2=78%). Herbal therapy (RR=1.57, 95% CI: 1.31 to 1.88, I2=77%), dietary supplements (RR=1.95, 95% CI: 1.02 to 3.73, I2=75%), and mind-body based therapy (RR=1.67, 95% CI: 1.13 to 2.49, I2=63%) showed benefit for overall response compared to placebo (low confidence in estimates). Body-based and energy healing therapies demonstrated no significant benefit over placebo or sham for abdominal pain or overall response.CAM therapies such as herbal or dietary supplements and mind-body based approaches may be beneficial for abdominal pain and overall response in IBS. However, overall quality of evidence is low. Rigorous, high quality clinical trials are warranted to investigate CAM in IBS.