Adolescence is marked by major puberty-induced changes including increased reactivity to stress and a peak incidence of mental disorders. The implementation of early interventions during this developmental period is essential to prevent mental disorders. In this clinical trial, we examined the effects of a mindfulness-based intervention (MBI) on internalizing symptoms, affects, and emotion-regulation strategies in a nonclinical sample of young adolescents. Seventy adolescents (41 girls) from the general population, aged between 13 and 15 years, were enrolled in a randomized controlled trial (RCT) that compared an 8-week MBI designed for adolescents and a waiting list. Levels of stress, anxiety and depressive symptoms, positive and negative affects, as well as emotion regulation strategies were measured before and after the intervention (4.8 weeks ± 4 SD) using self-reported questionnaires. We found no effect of our MBI on all self-reported measures, including stress, anxiety, depression, and positive and negative affects, as well as an emotion regulation strategies. Trait mindfulness was negatively correlated with measures of stress, anxiety, and negative affects. The intervention was very well accepted (only one dropout) with a high degree of satisfaction among participants. Individual responses to the intervention were very heterogeneous. Mindfulness practice in non-help-seeking adolescents was very well received, but did not show any benefit on symptoms, affects, or emotion regulation. This is consistent with the literature suggesting a better response in clinical than in nonclinical samples. Longer-term effects remain to be investigated, as does the possibility of identifying individuals who respond best to this early intervention. Trial Registration: ClinicalTrials.gov identifier: NCT04711694.