Despite progress in research on evidence-based treatments (EBTs) for youth psychopathology, many youths with mental health needs do not receive services, and EBTs are not always effective for those who access them. Wise interventions (WIs) may help address needs for more disseminable, potent youth mental health interventions. WIs are single-component, social-psychological interventions designed to foster adaptive meaning-making. They have improved health-related and interpersonal youth outcomes, yet their potential to reduce youth psychopathology has not been systematically explored. Accordingly, we conducted a systematic, descriptive review characterizing WIs' potential to reduce youth mental health problems. Across 25 RCTs (N=9,219 youths, ages 11-19) testing 13 intervention types, 7 WIs qualified as "Well-Established," "Probably Efficacious," or "Possibly Efficacious" for reducing one or more types of youth psychopathology, relative to controls. Among these, 5 WIs significantly reduced youth depressive symptoms; 3, general psychological distress; and 1 each, eating problems, anxiety, and substance use. Three of these 7 WIs were self-administered by youths, and four by trained interventionists; collectively, they were 30-168 minutes in length and targeted clinic-referred and nonreferred samples in clinical, school, and laboratory settings. Overall, certain WIs show promise in reducing mild to severe youth psychopathology. Given their brevity and low cost relative to traditional (i.e. therapist-delivered, 12-to-16 week, clinic-based) EBTs, WIs may represent beneficial additions to the youth mental healthcare ecosystem. Priorities for future research are proposed, including testing WIs for parents, younger children, and externalizing problems; as EBT adjuncts; and in schools and primary care clinics to increase access to brief, effective supports.