This meta-analysis evaluated the clinical efficacy of regenerative therapies for periodontal treatment, focusing on clinical attachment level gain and probing pocket depth reduction. A comprehensive literature search was conducted across Web of Science, Scopus, PubMed, Cochrane Library, and Google Scholar. Thirty-one studies published between 2019 and 2025 were included. Data analyses were performed using RevMan 5.4. The studies followed a PRISMA approach to ensure systematic reporting and consistency in methodology. The pooled results demonstrated that regenerative interventions significantly improved CAL gain (MD: 0.41 mm; 95% CI: 0.12-0.70; I² = 78%), with platelet derivatives (MD: 0.45 mm; 95% CI: 0.04-0.86; I² = 54%) and hydrogel-based therapies (MD: 0.53 mm; 95% CI: 0.03-1.04; I² = 71%) showing the most consistent benefits. PPD reduction was modest (MD: 0.06 mm; 95% CI: -0.23-0.35; I² = 84%), with platelet derivatives providing better outcomes (MD: 0.38 mm; 95% CI: -0.13-0.89; I² = 67%). Growth factor interventions improved CAL (MD: 0.21 mm; 95% CI: -0.26-0.67; I² = 48%) but showed variable PPD outcomes, while biomaterial-based scaffolds showed limited efficacy. Growth factor therapies improved CAL but produced variable PPD changes. Overall, findings support hydrogel- and platelet-based regeneration, highlighting the need for combined strategies, digital guidance, and extended follow-up for durable clinical outcomes.
