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Introduction: The regeneration of periodontal intrabony defects represents a relevant clinical challenge due to their anatomical complexity and the unpredictability of regenerative outcomes. Hyaluronic acid, a key component of the extracellular matrix, has been proposed as an adjunctive agent in periodontal regenerative therapies. Objectives: To critically analyze the available scientific evidence on the clinical and radiographic efficacy of hyaluronic acid in the regenerative treatment of periodontal intrabony defects. Methodology: An integrative literature review was conducted using the PubMed, Web of Science, Cochrane Library, and B-On databases, including studies published between 2018 and 2025. The search strategy combined MeSH terms and the keywords related to hyaluronic acid and periodontal regeneration following PRISMA guidelines; 11 studies were included. Results: The use of hyaluronic acid, particularly as an adjunctive agent, is associated with significant improvements in clinical periodontal parameters, clinical attachment level gain and probing pocket depth reduction, as well as radiographic evidence of bone fill in specific contexts. When combined with open flap debridement, hyaluronic acid demonstrated additional clinical benefits, particularly in the short term. In minimally invasive approaches and when compared with enamel matrix derivatives, a positive effect was mainly observed during the early healing phases, without sustained differences in the medium term. Discussion: Current evidence suggests that hyaluronic acid improves periodontal regenerative outcomes, particularly during early healing, but its long-term benefits remain uncertain. While hyaluronic acid appears to be a promising adjunctive therapy and a potential alternative to enamel matrix derivatives, further high-quality studies are needed to confirm its clinical effectiveness. Conclusion: Hyaluronic acid appears to be a promising adjunctive therapeutic option in the regenerative treatment of periodontal intrabony defects, contributing to improvements in clinical parameters and to the optimization of early healing.