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Introduction Endometriosis, a chronic oestrogen-dependent disorder, presents significant clinical challenges including pelvic pain, dysmenorrhoea, dyspareunia and infertility. While numerous interventions exist, evidence guiding the choice among surgical, hormonal and non-hormonal therapies is fragmented. This protocol outlines a systematic review and network meta-analysis designed to comprehensively evaluate the comparative effectiveness and safety of all available treatments for endometriosis-associated pain and infertility.Methods We will systematically search PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and WHO International Clinical Trials Registry Platform. Randomised controlled trials evaluating any intervention for endometriosis will be identified through a two-stage independent screening process by two reviewers. Primary outcomes are overall pain reduction and live birth rate. Secondary outcomes include clinical pregnancy rate, miscarriage rate, endometriosis recurrence, relief of other endometriosis-related symptoms, adverse events, quality of life and obstetrical outcomes. Data will be synthesised using pairwise and network meta-analyses.Ethics and dissemination This systematic review of published literature does not require ethical approval. Results will be disseminated through peer-reviewed publication. The findings aim to establish a robust evidence base for clinical decision-making and to inform future research priorities in endometriosis management.PROSPERO registration number CRD420251051917.