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Abstract Background Non-binary identities are increasingly recognized within the spectrum of gender diversity, yet there is a dearth of research exploring the mental health challenges specific to this population. Therefore, this systematic review and meta-analysis aimed to comprehensively assess the mental health outcomes of non-binary youth in comparison to their transgender and cisgender peers. Methods A systematic search was conducted to identify relevant studies across three electronic databases (PubMed, Scopus, Web of Science) covering the period from inception to October 2023. The meta-analysis was performed employing a random-effects model. Inclusion criteria encompassed studies comparing non-binary youth with transgender or cisgender youth, providing data on mental health outcomes such as general mental health, depressive and anxiety symptoms, self-harm and suicidality. Results Twenty-one studies, meeting the inclusion criteria and originating from six different countries, were included in the analysis. The sample encompassed 16,114 non-binary, 11,925 transgender, and 283,278 cisgender youth, with ages ranging from 11 to 25 years. Our meta-analysis revealed that non-binary youth exhibit significantly poorer general mental health compared to both transgender (d = 0.24, 95% CI, 0.05–0.43, p =.013) and cisgender youth (d = 0.48, 95% CI, 0.35–0.61, p