Objective To explore the effect of 3D surgical guide combined with minimally invasive corticalosteotomy in orthodontic treatment of skeletal Class Ⅱ malocclusion. Methods A total of 82 patients with skeletal Class Ⅱ malocclusion who received orthodontic treatment in the Department of Stomatology, the Affiliated Hospital of Xuzhou Medical University from January 2021 to January 2024 were selected, and they were divided into the control group and the observation group by the random number table method, with 41 patients in each group. The control group was given conventional flapped corticalosteotomy, and the observation group was given 3D surgical guide combined with minimally invasive corticalosteotomy. The tooth alignment time, space closure time, gingival crevicular fluid inflammatory factor levels and periodontal health status were compared between the two groups. Results The tooth alignment time and space closure time in the observation group were shorter than those in the control group (P <0.05). After treatment, the levels of IL-1β, IL-6 and sICAM-1 in gingival crevicular fluid of the observation group were lower than those of the control group (P <0.05). After treatment, the PD, GI, SBI and PLI of the observation group were lower than those of the control group (P <0.05). Conclusion The application of 3D surgical guide combined with minimally invasive corticalosteotomy in the orthodontic treatment of skeletal Class Ⅱ malocclusion can improve treatment effect, shorten the time required for tooth alignment and space closure, reduce the levels of inflammatory factors in gingival crevicular fluid, and help to improve patients’ periodontal health.