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Dental anxiety is common among children and frequently leads to avoidance of dental treatment, premature tooth loss, and broader health concerns such as bite misalignment. This systematic review examines nitrous oxide-oxygen (N₂O/O₂) and oral sedation (e.g., midazolam, hydroxyzine) as minimally invasive options for children aged 2-12 years, using the Patient/Population, Intervention, Comparison, and Outcome (PICO) framework to guide analysis. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, we searched PubMed, Cochrane, and Scopus (2015-2025), including 25 studies (n≈12,500 participants) with randomized controlled trials (RCTs), cohorts, and reviews. Risk of bias was assessed via Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) and A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2); qualitative synthesis was chosen due to heterogeneity. N₂O excelled in mild anxiety (85-92% efficacy, <5% complications like nausea, rapid 30-60 s onset), making it ideal for short procedures with full recovery in five minutes. Oral sedation showed 70-85% success for moderate cases, with midazolam offering strong amnesia but 5-10% paradoxical excitation; hydroxyzine suited low-risk adjuncts. Combinations boosted outcomes to 88-95%, cutting dropouts by 40-50%. Safety was high overall (<5% adverse events), with N₂O safer for outpatient use. Limitations include protocol variability and limited RCTs. Aligned with the American Academy of Pediatric Dentistry (AAPD) guidelines, these methods promote tailored, office-based care to enhance equity and reduce general anesthesia (GA) needs. Future RCTs should standardize metrics and explore adjuncts like dexmedetomidine. In practice, integrating with behavioral techniques fosters better cooperation and lifelong oral health.