Purpose <p>To evaluate the clinical outcomes of interproximal enamel reduction (IPR) in the permanent dentition amongst children and adolescents undergoing orthodontic treatment, focusing on enamel integrity, periodontal health and dimensional changes.</p> Methods <p>A systematic review was conducted using Embase, Medline, Web of Science, and manual research to identify publications between 1970 and October 2024 reporting on IPR outcomes in patients aged 8–17 years. Ten studies met the inclusion criteria: two cohort studies, one case–control study, and seven case reports. Most assessed immediately post-treatment, and few reported follow-up ranging from 3 to 15 years (mean: 5.71 years; median: 3.67 years). Clinical parameters such as enamel integrity, caries incidence, and periodontal status were used as proxies for safety. Data on IPR indications, treatment techniques, and clinical outcomes were analysed. Risk of bias was assessed using Newcastle–Ottawa and Murad tool. PROSPERO ID: CRD420251007607.</p> Results <p>The 10 articles analysed included 61 participants (mean age: 13.4 ± 1.71 years). Primary IPR indications were dental crowding (57.4%), followed by tooth reshaping (42.6%) and tooth-size-arch-size discrepancies (3.3%). Fixed appliances were used in 72.1% of cases. Mandibular anterior teeth were the most frequently treated (67.2%), followed by maxillary anterior (49.2%), mandibular posterior (37.5%), and maxillary posterior teeth (29.5%), with an average of 0.3 mm reduction per surface. No significant differences were observed between IPR and non-IPR groups regarding enamel and periodontium. Post-orthodontic arch dimensions remained stable, with minimal mandibular anterior relapse.</p> Conclusion <p>IPR appears to be a feasible adjunct for managing mild to moderate crowding in young patients. Further long-term studies are recommended.</p>