INTRODUCTION: Disparities in mental health services in low- and middle-income countries (LMIC) profoundly affect adolescent's well-being. To address this issue, the Early Adolescent Skills for Emotions (EASE) program may offer enhanced psychological support. Therefore, this study assessed the efficacy of EASE compared to Enhanced Treatment as Usual (ETAU) in adolescents aged 10 to 15 years living in LMIC and experiencing psychological distress. METHODS: We performed a systematic review with meta-analyses of randomized controlled trials (RCTs), registered in PROSPERO (CRD42024564497). We searched PubMed, Embase, PsycINFO, and Cochrane. The outcomes of interest included the Pediatric Symptom Checklist-Total (PSC-T), with Internalization (PSC-I) as primary outcome, along with Attention (PSC-A), Externalization (PSC-E), and well-being measures (WEMWBS and SWEMWBS). RESULTS: We included seven RCTs. The groups that received EASE showed significantly reduced PSC-I scores compared with ETAU (MD =  - 0.38; 95% CI [- 0.63, -0.13]; P < 0.01). However, there were no significant differences between these groups in PSC-T (MD = 0.26; 95% CI [-2.35-1.84]; P = 0.81), PSC-E (MD = -0.02; 95% CI [- 0.56-0.51]; P = 0.93), PSC-A (MD = -0.04; 95% CI [- 0.53-0.45]; P = 0.88), and Well-being (SMD = -0.01; 95% CI [-0.14-0.13]; P = 0.86) scores. CONCLUSION: We found that EASE was an intervention that significantly reduced internalizing symptoms in adolescents when compared to ETAU. However, our study did not find that EASE was superior to ETAU in reducing externalizing symptoms, attention, or well-being.