Introduction: Self-harm and non-suicidal self-injury (NSSI) are major mental health concerns, particularly among adolescents and young adults. Emotion dysregulation is increasingly recognized as a core mechanism underlying self-harming behavior; however, evidence on emotion regulation-based interventions and their effects on psychological and spiritual well-being remains fragmented. Methods: This systematic review followed the PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251232299). Searches were conducted in PubMed, PsycINFO, Scopus, and Web of Science for empirical intervention studies published from January 2015 to May 2025. Eligibility was structured using the Population, Intervention, Comparator, and Outcomes framework. Study quality was appraised using design-appropriate tools, including the RoB 2, ROBINS-I, and Joanna Briggs Institute checklists. A narrative synthesis was conducted because of clinical and methodological heterogeneity. Results: The strongest and most consistent evidence was found for dialectical behavior therapy-based and emotion regulation-focused interventions. These approaches generally reduce NSSI frequency, self-harm, suicidal behaviors, and emotion dysregulation. Adolescent studies most strongly supported dialectical behavior therapy for adolescents and internet-delivered emotion regulation individual therapy, whereas adult studies mainly supported emotion regulation group therapy and dialectical behavior therapy skills training. Psychological outcomes improved but remained heterogeneous, whereas spiritual well-being was rarely measured directly. Conclusions: Emotion regulation-based interventions may support mental health nursing care for self-harm prevention, psycho-education, safety planning, and follow-up. Stronger trials with standardized psychological and spiritual outcomes are needed.