BACKGROUND: HIV-related stigma negatively impacts HIV prevention, treatment, and care, particularly among children and adolescents in sub-Saharan Africa. Interventions that are culturally grounded and relevant for addressing root causes may reduce the stigma experienced by HIV-positive and HIV-affected young people. This study, to be conducted in a post-conflict, rural setting in Omoro District, Uganda, will develop and evaluate a transformative  arts-based HIV-related stigma intervention rooted in local cultural knowledge to reduce stigma and improve HIV prevention and care for young people living with HIV. The intervention will be delivered to young people attending school by community Elders, with the support of teachers, through the transfer of local cultural knowledge and practices with the aim of re-establishing the important cultural and social role of Elders within a community that has suffered the loss of intergenerational transfer of cultural knowledge throughout a 25-year civil war. METHODS: A formative research phase consisting of interviews with students, teachers, and Elders will inform the intervention and provide data for study objectives. Workshops will be delivered to Elders and teachers in participating schools to build capacity for arts-based, educational workshops to be conducted with students in the classroom. The intervention will be evaluated using a stepped-wedge cluster-randomized trial. Government-funded schools in Omoro District will be randomized into three blocks, each comprised of two primary and two secondary schools (n=1800 students). Schools will be randomly assigned to a crossover sequence from control to intervention condition in 8-week intervals. A process evaluation will be implemented throughout the study to evaluate pathways between intervention development, implementation, and effects. DISCUSSION: This study will generate comprehensive, in-depth participatory research and evaluation data to inform an effective and sustainable protocol for implementing arts-based HIV stigma interventions for young people in school settings. Findings will have widespread implications in post-conflict settings for HIV prevention, treatment, and care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04946071 . Registered on 30 June 2021.