BACKGROUND: Stigma is a barrier to inclusion for people with disabilities and mental health conditions. There is increasing recognition of the need to address stigma within disability inclusive programmes, but limited research is available on what are effective participatory approaches to stigma reduction interventions. OBJECTIVES: (1) To document participatory approaches used in the design and delivery of disability stigma reduction interventions in a disability and mental health programme in Ghana and (2) to understand the experience of programme implementers and participants in these processes, with particular attention to the leadership and involvement of people with disabilities. METHOD: A mixed-methods study was conducted. The data were drawn from a purposive sample of 20 in-depth interviews (IDIs) with programme staff, partners and key stakeholders, and 12 focus group discussions (FGDs) with self-help group (SHG) members, organisation of people with disabilities (OPD) members, and disability champions. We conducted thematic analysis using deductive and inductive approaches. RESULTS: The programme adopted several approaches to participation at design and implementation stages, with a focus on the leadership of people with disabilities and people with mental health conditions. The process was seen to promote acceptability of stigma reduction approaches. Providing opportunities for building and strengthening relationships with a wide range of stakeholders was key to successful implementation. Understanding, and engaging with, power dynamics in the local context also provided important benefits. CONCLUSIONS: Participation of people with disabilities and mental health conditions is essential for the design and delivery of stigma reduction programmes in Ghana. CONTRIBUTION: This study provided lessons from the field on the value of participation in reducing stigma, and the role of key stakeholders, particularly people with disabilities and mental health conditions.