This systematic review examines the application of clear aligners in managing mixed dentition, a critical phase in pediatric oral development characterized by the coexistence of primary and permanent teeth. The primary objective is to evaluate the efficacy, safety, and acceptability of aligner therapy in this age group. The review focuses on randomized controlled trials, cohorts, and observational studies, considering clinical, radiographic, and psychosocial parameters to assess the overall impact of aligner therapy. The review aims to provide a comprehensive overview of the potential of clear aligners in pediatric orthodontics, contributing to the development of practical guidelines and targeted therapeutic strategies. It also identifies gaps in current research and suggests future directions for studies, contributing to the ongoing evolution of evidence-based orthodontic practices. Key findings highlight the effectiveness, safety, and acceptability of aligners in treating various malocclusions, expanding the maxillary arch, and addressing Class II malocclusions, while also improving gingival and periodontal health. However, the review notes limitations such as heterogeneity among studies and the need for larger randomized controlled trials to enhance understanding and optimize treatment outcomes.This systematic review examines the application of clear aligners in managing mixed dentition, a critical phase in pediatric oral development characterized by the coexistence of primary and permanent teeth. The primary objective is to evaluate the efficacy, safety, and acceptability of aligner therapy in this age group. The review focuses on randomized controlled trials, cohorts, and observational studies, considering clinical, radiographic, and psychosocial parameters to assess the overall impact of aligner therapy. The review aims to provide a comprehensive overview of the potential of clear aligners in pediatric orthodontics, contributing to the development of practical guidelines and targeted therapeutic strategies. It also identifies gaps in current research and suggests future directions for studies, contributing to the ongoing evolution of evidence-based orthodontic practices. Key findings highlight the effectiveness, safety, and acceptability of aligners in treating various malocclusions, expanding the maxillary arch, and addressing Class II malocclusions, while also improving gingival and periodontal health. However, the review notes limitations such as heterogeneity among studies and the need for larger randomized controlled trials to enhance understanding and optimize treatment outcomes.