Objective To analyze the effect of periodontal tissue regeneration (PTR) combined with invisible orthodontic treatment without brackets in patients with periodontitis and malocclusion. Methods A total of 94 patients with periodontitis and malocclusion admitted to our hospital from February 2019 to March 2021 were selected as the research objects. According to the random number table method, they were divided into study group and control group, with 47 patients in each group. Both groups were treated with PTR. The control group was treated with straight wire appliance, and the study group was treated with invisible orthodontic treatment without brackets. The periodontal indexes, inflammatory factor levels and complications were compared between the two groups. Results After treatment, the gingival index (GI), periodontal pocket probing depth (PD) and clinical attachment loss (CAL) in the study group were lower than those in the control group, and the differences were statistically significant (P<0.05). After treatment, the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the study group were lower than those in the control group, the differences were statistically significant (P<0.05). The incidence of complications in the study group was 2.13%, which was lower than 17.20% in the control group, the difference was statistically significant (P<0.05). Conclusion The application of PTR combined with invisible orthodontic treatment without brackets in patients with periodontitis and malocclusion is effective, which can effectively reduce the level of inflammatory factors, improve the periodontal index, and the application safety is high.