Background Mental health issues in youths have cascading negative effects on school outcomes, professional life, and physical health. Psychological well-being (P-WB) is an important protective factor against mental illness. Methods Preliminary research suggests that mindfulness- and yoga-based socio-emotional learning (SEL) interventions can each have a positive impact on preschoolers P-WB. The objective of this trial is to rigorously evaluate the effect of a 24-week combined mindfulness- and yoga- based SEL intervention in preschool children from a French socio-economically disadvantaged area. The P-WB promotion intervention is compared to a wait-list control condition in a cluster randomized controlled trial (RCT). Sixty-four pre-Kindergarten classrooms are randomized to the intervention or control group. Primary outcomes measure self-management capacity and core P-WB components: connection, insight, engagement, and positive relationship. Secondary outcomes include measures of mental health, executive functioning, and school performance. Primary and secondary outcomes are assessed through teacher questionnaires, standardized observations of children in school context, and experimental tasks and by collecting results of the national evaluation at first grade. All children-level outcomes are evaluated at pre-intervention, at the end of the intervention, and 1 year later (follow-up analysis), to the exception of school performance which is evaluated at follow-up only. Discussion This is the first trial to rigorously evaluate a combined mindfulness- and yoga-based P-WB promotion intervention, and the first RCT evaluating a SEL curriculum in French schools. Results may have key implications for P-WB promotion in preschool children. Trial Registration https://www.drks.de/ DRKS00028623. Retrospectively registered on 30 May 2022