In recent years, there has been a notable increase in the prevalence of deliberate self-harm (DSH) among adolescents, which has led to the recognition of this issue as a significant public health challenge. However, school-based prevention programmes for DSH remain scarce. This study aimed to develop, implement, and evaluate the effectiveness of the Healthy Minds programme, a universal school-based prevention intervention targeting DSH in adolescents. Conducted in a Lisbon school, the programme sought to reduce DSH and suicidal ideation, change beliefs about DSH, and promote help-seeking. A quasi-experimental design with experimental and control groups included 137 participants aged 13-19 (M = 14.73; SD = 1.03), assessed at three time points: pre-intervention, post-intervention, and follow-up. The intervention showed partial effectiveness, with delayed reductions in DSH and significant improvements in reducing false beliefs. In addition, both groups showed increased help-seeking behaviours, and these effects were sustained over the follow-up period, suggesting long-term effectiveness. However, no significant improvements were observed in the ability to recognise warning signs of DSH, nor were there reductions in levels of suicidal ideation. The Healthy Minds programme shows promise in reducing DSH, improving mental health literacy and promoting help-seeking behaviours in adolescents, with sustained benefits observed over time. These findings highlight the importance of implementing well-structured, methodologically robust school-based interventions aimed at preventing DSH in this population. To maximise programme effectiveness, longer follow-up periods and more integrated, multifaceted approaches are essential.