Background: Peer support is an established intervention involving a person recovering from mental illness to support others with mental illness.. Peers are an under-used resource in global mental health. Building upon comprehensive formative research, this study will rigorously evaluate the impact of peer support at multiple levels, including: service user outcomes (psychosocial and clinical); peer support worker outcomes (work role, empowerment); service outcomes (cost-effectiveness, return on investment); and implementation outcomes (adoption, sustainability, organisational change). Methods: UPSIDES-RCT is a pragmatic parallel-group multi-centre randomised controlled trial assessing the effectiveness of UPSIDES at four measurement points over one year (baseline, 4-, 8-, and 12-month follow-up), with embedded process evaluation and cost-effectiveness analysis. Research will take place in a range of high-, middle- and low-income countries (Germany, United Kingdom, Israel, India, Uganda, Tanzania). The primary outcome is social inclusion of service users with severe mental illness (N= 558; N = 93 per site) at 8-month follow-up, measured with the Social Inclusion Scale. Secondary outcomes include empowerment (Empowerment Scale), hope (HOPE scale), recovery (Stages of Recovery), and health and social functioning (Health of the Nations Outcome Scales). Mixed-methods process evaluation will investigate mediators and moderators of effect, and implementation experiences of four UPSIDES stakeholder groups (service users, peer support workers, mental health workers, policy makers). A cost-effectiveness analysis examining cost-utility and health budget impact will estimate the value for money of UPSIDES peer support. Discussion: The UPSIDES-RCT will explore the essential components necessary to create a peer support model in mental health care, while providing the evidence required to sustain and eventually scale-up the intervention in different cultural, organisational and resource settings. By actively involving and empowering service users, UPSIDES will move mental health systems toward a recovery orientation, emphasising user-centeredness, community participation, and the realisation of mental health as a human right.