Background <p>There is robust evidence reflecting that individuals with PTSD are significantly more at risk of engaging in self-harm and suicidal behaviours. Trauma-focused interventions for PTSD, however, predominantly focus on PTSD symptomology-related outcomes. Therefore, there is a dearth of knowledge regarding the treatment effects of psychological interventions in individuals with PTSD examining self-harm-related outcomes. This evidence synthesis will identify studies that investigate interventional effects on self-harm, non-suicidal self-injury (NSSI), and suicide attempts.</p> Methods <p>A comprehensive bibliographic search will be conducted to identify eligible randomised controlled trials (RCTs) and non-RCT evaluation studies indexed in Ovid MEDLINE, Embase (Ovid), PTSDPubs (ProQuest), APA PsycInfo (Ovid), PubMed (NOT MEDLINE[SB]), Web of Science Core Collection (CPCI-SSH), CENTRAL, WHO ICTRP, and ClinicalTrials.gov from inception to present day. A range of supplementary search techniques will also be employed to reduce the file drawer effect. Two independent reviewers will screen records at a title/abstract and full-text level, with 50% extracted data being cross-checked by an independent reviewer. Eligible studies will be assessed for risk-of-bias (RoB) using Cochrane’s RoB 2.0 for RCTs and ROBINS-I for non-RCTs. A combination of random- and fixed-effects meta-analytic models will be performed separately for RCTs and non-RCTs, and for post-intervention and follow-up periods for self-harm, NSSI, and suicide attempts separately and in aggregate, using <i>d</i>-family effect sizes (including Hedges’ <i>g</i>) and risk ratio/odds ratio for continuous and binary outcome data, respectively, with associated 95% confidence intervals. Sensitivity analyses will be performed to examine if methodological decisions impact on summary effects. Potential sources of heterogeneity will be examined as moderators (e.g. adults versus non-adults, intervention delivery, and complex PTSD versus PTSD) using mixed-effect meta-regression models. The evaluation of certainty of evidence of all main outcomes will be conducted using the GRADE approach. The review will be reported in accordance with PRISMA-S and PRISMA 2020 guidelines.</p> Discussion <p>This systematic review and meta-analysis of RCTs and non-RCTs will provide a comprehensive synthesis of treatment effects of psychological interventions on self-harm related outcomes among individuals with PTSD. The results may increase a better understanding of which interventions are best suited to targeting self-harm outcomes in this population. The completed review will be published in a peer-reviewed journal.</p> Systematic review registration <p>PROSPERO CRD42024598594</p>