Historically, religion has had a central role in shaping the psychosocial and moral development of young people. While religiosity and spirituality have been linked to positive mental health outcomes in adults, their role during the developmental context of adolescence, and the mechanisms through which such beliefs might operate, is less well understood. Moreover, there is some evidence that negative aspects of religiosity are associated with poor mental health outcomes. Guided by lived experience consultants, we undertook a systematic review and quality appraisal of 45 longitudinal studies and 29 intervention studies identified from three electronic databases (Medline, PsycINFO and Scopus) exploring the role of religiosity and spiritual involvement (formal and informal) in prevention and management of depression and anxiety in young people aged 10 to 24 years. Most studies were from high-income countries and of low to moderate quality. Meta-analysis of high-quality longitudinal studies (assessed using Joanna Briggs Institute critical appraisal tools, n = 25) showed a trend towards association of negative religious coping (i.e., feeling abandoned by or blaming God) with greater depressive symptoms over time (Pearson’s r = 0.09, 95% confidence interval (CI) -0.009, 0.188) whereas spiritual wellbeing was protective against depression (Pearson’s r = -0.153, CI -0.187, -0.118). Personal importance of religion was not associated with depressive symptoms overall (Pearson’s r = -0.024, CI-0.053, 0.004). Interventions that involved religious and spiritual practices for depression and anxiety in young people were mostly effective, although the study quality was typically low and the heterogeneity in study designs did not allow for a meta-analysis. The lived experience consultants described spirituality and religious involvement as central to their way of life and greatly valued feeling watched over during difficult times. While we require more evidence from low- and middle-income countries, in younger adolescents and for anxiety disorders, the review provides insight into how spirituality and religious involvement could be harnessed to design novel psychological interventions for depression and anxiety in young people.Review RegistrationThe systematic review was funded by Wellcome Trust Mental Health Priority Area 'Active Ingredients' 2021 commission and registered with PROSPERO 2021 (CRD42021281912).