Background <p>There are no established evidence-based guidelines for the administration of intraoperative local anesthesia (LA) during dental rehabilitation under general anesthesia (GA). This systematic review aims to evaluate the effects of intraoperative LA on physiological parameters and pain control in children undergoing GA for comprehensive dental treatment.</p> Methods <p>Comprehensive search was conducted across four electronic databases: PubMed, Cochrane Central Register of Controlled Trials, EBSCO, and Scopus. Search strategy was structured, yielding 14 articles that follow the study inclusion criteria. Risk of bias was performed using Cochrane Collaboration's tool for randomized trials and confidence of recommendation according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Whenever there were sufficient studies with comparable data, meta-analysis was performed.</p> Results <p>Pain levels were significantly lower in the LA group compared to controls (OR = 0.32, 95% CI 0.14–0.70, <i>P</i> = 0.005). Lip and/or cheek biting occurred more frequently in the LA group, though this difference was not statistically significant. Although reductions were observed in physiological parameters, only the decrease in end-tidal CO₂ volume reached statistical significance (<i>P</i> = 0.02). The included studies were rated as having low confidence and quality based on the GRADE assessment.</p> Conclusion <p>While the intraoperative use of LA under GA reduced postoperative pain and end-tidal CO₂ volume, other effects were negligible, making its routine use optional. Evidence suggests targeting LA for high-pain procedures, such as multiple extractions, while exercising caution or withholding it during deep sedation to mitigate potential drops in tidal volume.</p> Systematic review registration <p>PROSPERO CRD42022340846</p>