ObjectiveTo summarise the available clinical evidence on the efficacy and safety of osteopathic manipulative treatment (OMT) for different conditions.DesignOverview of systematic reviews (SRs) and meta-analyses (MAs). PROSPERO CRD42020170983.Data sourcesAn electronic search was performed using seven databases: PubMed, EMBASE, CINAHL, Scopus, JBI, Prospero and Cochrane Library, from their inception until November 2021.Eligibility criteria for selecting studiesSRs and MAs of randomised controlled trials evaluating the efficacy and safety of OMT for any condition were included.Data extraction and synthesisThe data were independently extracted by two authors. The AMSTAR-2 tool was used to assess the methodological quality of the SRs and MAs. The overview was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.ResultsThe literature search revealed nine SRs or MAs conducted between 2013 and 2020 with 55 primary trials involving 3740 participants. The SRs reported a wide range of conditions including acute and chronic non-specific low back pain (NSLBP, four SRs), chronic non-specific neck pain (CNSNP, one SR), chronic non-cancer pain (CNCP, one SR), paediatric (one SR), neurological (primary headache, one SR) and irritable bowel syndrome (IBS, one SR). Although with a different effect size and quality of evidence, MAs reported that OMT is more effective than comparators in reducing pain and improving functional status in acute/chronic NSLBP, CNSNP and CNCP. Due to small sample size, presence of conflicting results and high heterogeneity, questionable evidence existed on OMT efficacy for paediatric conditions, primary headache and IBS.No adverse events were reported in most SRs. According to AMSTAR-2, the methodological quality of the included SRs was rated low or critically low.ConclusionBased on the currently available SRs and MAs, promising evidence suggests the possible effectiveness of OMT for musculoskeletal disorders. Limited and inconclusive evidence occurs for paediatric conditions, primary headache and IBS. Further well-conducted SRs and MAs are needed to confirm and extend the efficacy and safety of OMT.