Objective To explore the effect of periodontal guided tissue regeneration technique on periodontal indicators in patients with moderate to severe periodontitis. Methods A total of 60 patients with moderate to severe periodontitis admitted to Lianyungang 149 Hospital from May 2023 to October 2025 were selected, and they were divided into the reference group and the study group by the random number table method, with 30 patients in each group. The reference group was treated with conventional ffap surgery, and the study group was treated with periodontal guided tissue regeneration technique. The treatment effect, periodontal indicators, quality of life, alveolar bone indicators and dental aesthetics were compared between the two groups. Results The total effective rate of treatment in the study group (96.67%) was higher than that in the reference group (73.33%) (P<0.05). After treatment, the gingival index, plaque index and sulcus bleeding index of the study group were lower than those of the reference group (P<0.05). After treatment, the scores of GOHAI scale in the study group were lower than those in the reference group (P<0.05). After treatment, the alveolar bone width, height and bone mineral density of the study group were higher than those of the reference group (P<0.05). After treatment, the score of PES in the study group was higher than that in the reference group (P<0.05). Conclusion The application of periodontal guided tissue regeneration technique in patients with moderate to severe periodontitis has deffnite advantages. It can effectively improve the overall treatment effect, optimize periodontal indicators, further enhance alveolar bone indicators, improve dental aesthetics and patients' quality of life, which is worthy of clinical application.