Objective To investigate the effect of guided tissue regeneration (GTR) combined with orthodontic treatment on periodontal indicators in patients with malocclusion complicated with periodontal disease. Methods A total of 78 patients with malocclusion complicated with periodontal disease admitted to Suzhou Stomatological Hospital from January 2023 to April 2024 were selected, and they were divided into the control group (n=39) and the study group (n=39) by the random number table method. Both groups received basic periodontal treatment. The control group received orthodontic treatment, and the study group received GTR treatment on the basis of the control group. The clinical efffcacy, periodontal indicators, aesthetics and oral health status were compared between the two groups. Results The total effective rate of treatment in the study group was 97.44%, which was higher than 79.49% in the control group (P<0.05). After treatment, the PD and AL of the study group were lower than those of the control group (P<0.05). After treatment, the scores of PES and WES in the study group were higher than those in the control group (P<0.05). After treatment, the OHIP-14 score of the study group was lower than that of the control group (P<0.05). Conclusion GTR combined with orthodontic treatment for patients with malocclusion complicated with periodontal disease can improve clinical efffcacy, optimize periodontal indicators, and enhance dental aesthetics and oral health level.