Objective To analyze the effect of microscopic apical surgery on periodontal indicators and inflammatory factor levels in patients with periodontal-endodontic combined lesions. Methods A total of 90 patients with periodontal-endodontic combined lesions admitted to the Department of Stomatology, the Third Hospital of Handan from January 2024 to January 2025 were selected as the research subjects, and they were divided into the reference group and the experimental group by the random number table method, with 45 patients in each group. The reference group was treated with traditional surgical apical surgery, and the experimental group was treated with microscopic apical surgery. The apical lesion healing, periodontal indicators, inffammatory factor levels and complication rate were compared between the two groups. Results The complete healing rate of the experimental group was higher than that of the reference group (P<0.05). The scores of PLI and GBI in the experimental group at 30 days after surgery were lower than those in the reference group (P<0.05). The levels of TNF-α and hs-CRP in the experimental group at 30 days after surgery were lower than those in the reference group (P<0.05). The incidence of complications in the experimental group (8.89%) was lower than that in the reference group (26.67%) (P<0.05). Conclusion In the treatment of periodontal-endodontic combined lesions, microscopic apical surgery, with its advantage of precise operation, can improve periodontal-related clinical indicators, effectively down-regulate the expression level of local inffammatory factors, thereby promoting the healing of apical lesion areas and reducing the risk of postoperative complications.