OBJECTIVES: To identify and critically appraise published clinical practice guidelines (CPGs) regarding healthcare of gender minority/trans people. DESIGN: Systematic review and quality appraisal using AGREE II (Appraisal of Guidelines for Research and Evaluation tool), including stakeholder domain prioritisation. SETTING: Six databases and six CPG websites were searched, and international key opinion leaders approached. PARTICIPANTS: CPGs relating to adults and/or children who are gender minority/trans with no exclusions due to comorbidities, except differences in sex development. INTERVENTION: Any health-related intervention connected to the care of gender minority/trans people. MAIN OUTCOME MEASURES: Number and quality of international CPGs addressing the health of gender minority/trans people, information on estimated changes in mortality or quality of life (QoL), consistency of recommended interventions across CPGs, and appraisal of key messages for patients. RESULTS: Twelve international CPGs address gender minority/trans people's healthcare as complete (n=5), partial (n=4) or marginal (n=3) focus of guidance. The quality scores have a wide range and heterogeneity whichever AGREE II domain is prioritised. Five higher-quality CPGs focus on HIV and other blood-borne infections (overall assessment scores 69%-94%). Six lower-quality CPGs concern transition-specific interventions (overall assessment scores 11%-56%). None deal with primary care, mental health or longer-term medical issues. Sparse information on estimated changes in mortality and QoL is conflicting. Consistency between CPGs could not be examined due to unclear recommendations within the World Professional Association for Transgender Health Standards of Care Version 7 and a lack of overlap between other CPGs. None provide key messages for patients. CONCLUSIONS: A paucity of high-quality guidance for gender minority/trans people exists, largely limited to HIV and transition, but not wider aspects of healthcare, mortality or QoL. Reference to AGREE II, use of systematic reviews, independent external review, stakeholder participation and patient facing material might improve future CPG quality. PROSPERO REGISTRATION NUMBER: CRD42019154361.