Adolescence is a strategic developmental stage in terms of preventing later difficulties and ensuring good mental health. Prophylactic interventions, which are conducted before the onset, prolongation, or worsening of difficulties, and aim to prevent or reduce symptoms or to promote wellbeing, therefore appear particularly appropriate for adolescents. However, existing prophylactic interventions conducted with adolescents have several weaknesses, including sparse theoretical frameworks, ambivalent evidence of their efficacy, and implementation and dissemination difficulties. In addition, no data are currently available on the effectiveness of such interventions in France. To fill this gap, a four-arm randomized controlled trial will be performed to assess the effectiveness of three prophylactic interventions targeting reactive, proactive and interpersonal adaptation in fourth-grade middle-school students, together with participants’ experience and perception of the interventions. Based on existing knowledge about adolescents, their learning mechanisms, and field constraints, these three interventions have been designed to promote their learning and receptiveness to interventions. Compared with baseline (i.e., before the intervention), we expect to observe a significant decrease in the level of distress (anxiety and depressive symptoms, functional impairment, and psychosocial difficulties) and a significant increase in the level of wellbeing after the intervention, across the three intervention groups, but not in the control group. In addition, we expect to observe post-intervention improvements in the processes targeted by the reactive adaptation intervention (operationalized as coping strategy use and flexibility), those targeted by the proactive adaptation intervention (operationalized as the tendency to engage in committed actions and general self-efficacy), and those targeted by the interpersonal adaptation intervention (operationalized as assertiveness in interactions), but only in the corresponding groups, with no change in any of these processes in the control group. The results of this research will not only enrich our knowledge of the processes involved in adolescents’ distress and wellbeing, but also provide clues as to the best targets for intervention. Moreover, the material for these interventions will be freely available in French on request to the corresponding author, providing access to innovative and fully assessed interventions aimed at promoting adolescents’ mental health in France.This clinical trial is currently being registered under no. 2023-A01973-42 on https://ansm.sante.fr/. This is the first version of the protocol.