Background Loneliness is a common problem in young people (14-24 years) and predicts the onset of depression and anxiety. Interventions to reduce loneliness thus have significant potential as active ingredients in strategies to prevent or alleviate anxiety and depression among young people. In this review, we aimed to combine qualitative and quantitative evidence with stakeholder views to identify interventions that appear worth testing for their potential effectiveness in achieving this.Methods We conducted a critical interpretative synthesis, a systematic review method that iteratively synthesises qualitative and quantitative evidence and is explicitly focused on building theory through a critical approach to the evidence that questions underlying assumptions. Literature searches were performed using nine databases, and eight additional databases were searched for theses and grey literature. Charity and policy websites were searched for content relevant to interventions for youth loneliness. We incorporated elements of rapid realistic review approaches by consultating with young people and academic experts to feed into search strategies and the resulting framework, in which we aimed to set out which interventions appear potentially promising in terms of theoretical and empirical underpinnings and fit with stakeholder views.Findings Through synthesising 27 studies (total participants n=105,649; range 1-102,072 in different studies) and grey literature and iteratively consulting with stakeholders, a conceptual framework was developed. A range of Intrapersonal (e.g. therapy that changes thinking and behaviour), Interpersonal (e.g. improving social skills), and Social Strategies (e.g. enhancing social support, providing opportunities for social contact) seem worth testing further for their potential to help young people address loneliness, thereby preventing or alleviating depression and/or anxiety. Such strategies should be co-designed and personalised to fit individual needs. Plausible mechanisms of action are facilitating sustained social support, providing opportunities for young people to socialise with peers who share similar experiences, and changing thinking and behaviour, for instance through building positive attitudes to themselves and others.Interpretation Strategies to address loneliness and prevent or alleviate anxiety and depression need to be co-designed and personalised. Promising elements to incorporate into these strategies are social support, including from peers with similar experiences, and psychological therapy.