Mental health disorders among adolescents have risen significantly in recent years, particularly following the COVID-19 pandemic, highlighting the need for effective preventive and supportive interventions. Nurses play a key role in the promotion, early detection, and management of mental health issues in adolescents, both in school and community settings. This study aimed to synthesize quantitative and qualitative evidence on the role, effectiveness, and implementation of nursing interventions for adolescent mental health. A systematic mixed-methods review was conducted in accordance with the PRISMA 2020 guidelines. It was registered in PROSPERO (CRD42024502076). Databases including PubMed, Scopus, SciELO, Dialnet, BVS, and Cuiden were searched for studies published between 2014 and 2024. Twelve studies met the inclusion criteria, comprising randomized and non-randomized quantitative studies, qualitative studies, and previous reviews. The interventions identified included cognitive-behavioral therapy programs, resilience and life skills training, physical activity initiatives, digital interventions, and mental health literacy strategies. Overall, the findings suggest improvements in symptoms of anxiety and depression, coping skills, resilience, and knowledge about mental health, particularly in structured school-based programs. Qualitative evidence highlighted the importance of accessibility, multidisciplinary collaboration, cultural sensitivity, and sustained commitment for successful implementation. However, considerable heterogeneity was observed in study designs, interventions, and outcome measures. In conclusion, nursing interventions can make a positive contribution to adolescents’ mental health, particularly in school and community settings. However, further rigorous, long-term studies are needed to strengthen the evidence base.