Objectives <p>Mindfulness-based interventions (MBIs) for children and young people have gained recognition in enhancing their mental health. Understanding how MBIs may exert their effects is essential for optimizing mindfulness programs in young people. This systematic review and meta-analysis aimed to identify and synthesize mediators of MBIs in youngsters.</p> Method <p>A comprehensive search of PubMed, PsycINFO, Scopus, and EMBASE identified 4435 records published from January 2000 to November 2024. Forty-two studies involving 14,690 participants were included. Due to limited studies in children and adolescents, the meta-analyses focused on tertiary students. Narrative synthesis was also conducted.</p> Results <p>In tertiary students, trait mindfulness (<i>ES</i> =  − 0.15, 95% <i>CI</i> − 0.26 to − 0.04), mindful attention and awareness (<i>ES</i> =  − 0.12, 95% <i>CI</i> − 0.20 to − 0.05), mindful acceptance and decentering (<i>ES</i> =  − 0.16, 95% <i>CI</i> − 0.27 to − 0.05), and self-compassion (<i>ES</i> =  − 0.20, 95% <i>CI</i> − 0.32 to − 0.08) acted as mediators between MBIs and stress. Narrative synthesis found insufficient evidence to support the indirect effects of these mediators on other mental health outcomes for tertiary students. Mediation studies of self-regulation and biased self-processing generated mixed results. There was some but insufficient evidence to support the mediators on mental health of adolescents and children.</p> Conclusions <p>This review supported the benefits of MBIs through improved mindfulness skills and self-compassion in tertiary students’ mental health. More studies in children and adolescents were needed to compare whether mechanisms varied across age groups.</p> Preregistration <p>The review protocol was registered on PROSPERO (Registration No: CRD42023495622).</p>