: Objective: To explore the efficacy of root canal treatment combined with guided tissue regeneration (GTR) in treating patients with combined pulp and periodontal lesions. Methods: From December 2024 to December 2025, 90 patients with combined pulp and periodontal lesions were selected and randomly divided into two groups, with 45 cases in each group. The control group received traditional apical surgery treatment, while the observation group received root canal treatment combined with GTR. The therapeutic effects of the two groups were compared. Results: The clinical total effective rate of the observation group was higher than that of the control group (P < 0.05); the postoperative periodontal indicators and imaging assessment of the observation group were better than those of the control group (P < 0.05); the inflammatory factor levels of the observation group after surgery were lower than those of the control group (P < 0.05). Conclusion: Root canal treatment combined with GTR can effectively improve the clinical efficacy of combined pulp and periodontal lesions, improve periodontal indicators, promote the healing of apical lesions, increase alveolar bone density and new bone formation, reduce local inflammatory levels, and has good clinical application value.