The aim of this systematic review and meta-analysis was to evaluate the effectiveness of the osteopathic manipulative treatment (OMT) in adults with irritable bowel syndrome (IBS). A literature resview was carried out on the following databases: PubMed, Embase, Cochrane, Cinahl, Scopus, PEDro and ClinicalTrials.gov. 350 articles were recovered. Eligibility criteria were evaluated by two independent reviewers, including randomized controlled trials (RCTs), quasi-RCTs, or ongoing RCTs with OMT compared to any kind of control in patients diagnosed with IBS. Six studies (five RCTs and one ongoing RCT) were considered eligible. Four RCTs were classified as some concerns and one as high risk of bias. In the meta-analysis, OMT compared to sham/no intervention showed statistically significant results for abdominal pain (effect size ES = −1.14 [−1.66, −0.62]; p < 0.0001) and constipation (ES = −0.66 [−1.12, −0.20]; p = 0.005). Instead, OMT was not superior to the control for the IBS symptoms measured with the IBS Severity Score and the Likert scale (ES = −0.34 [−0.83, 0.16]; p = 0.19), and diarrhea (ES = −1.20 [−2.84, 0.43]; p = 0.15). The quality of evidence was “low” for IBS symptoms in general for abdominal pain and constipation, while it was judged as “very low” for diarrhea. OMT turns out to be safe in the treatment of IBS without major adverse effects. OMT may be effective in IBS patients, however the results must be interpreted carefully due to the low methodological quality of the studies.