Objective <p>To evaluate the effects of concentrated growth factors (CGFs) combined with Bio-Oss bone substitute on the periodontal healing of adjacent teeth following impacted tooth extraction.</p> Methods <p>This single-centre prospective controlled study enrolled 60 patients requiring bilateral impacted mandibular third molar extraction. Patients were randomly allocated to a test group (<i>n</i> = 30; extraction socket filled with CGFs + Bio-Oss and covered with a CGF membrane) or control group (<i>n</i> = 30; natural healing). Primary outcomes included periodontal probing depth (PD) and distal bone height measured by cone beam computed tomography at baseline and 3 and 6 months. Secondary outcomes comprised the visual analogue scale (VAS) pain scores, swelling assessment and dry socket incidence. Statistical analysis was performed using SPSS 26.0, with significance set at <i>P</i> &lt; 0.05.</p> Results <p>A total of 60 patients were enrolled in this randomised single-blind clinical trial. The test group showed significantly greater PD reduction (2.41 ± 0.89 vs. 1.52 ± 0.73&#xa0;mm, <i>P</i> &lt; 0.001) and bone height gain (2.87 ± 1.12 vs. 1.63 ± 0.91&#xa0;mm, <i>P</i> &lt; 0.001) at 6 months than the control group. The VAS pain scores were significantly lower in the test group at days 3 and 7 (<i>P</i> &lt; 0.001). No cases of dry socket occurred in the test group, compared with three cases (11.1%) in the control group. Multivariate analysis revealed that CGFs + Bio-Oss application was the strongest predictor of bone gain ≥ 2&#xa0;mm (β = 0.412, <i>P</i> &lt; 0.001).</p> Conclusion <p>Concentrated growth factors combined with Bio-Oss significantly enhance periodontal healing and bone regeneration at adjacent teeth following impacted tooth extraction while reducing postoperative complications. This combined approach represents a promising strategy for clinical practice.</p>