Objective: To study the efficacy of azithromycin orally combined with vaginal suppository topical administration in the treatment of non-gonococcal cervicitis and the effect on the pathogen conversion rate. Methods: 110 cases of patients with nongonococcal cervicitis in the First Affiliated Hospital of Nanyang Medical College of Higher Specialized Sciences in our hospital were included from January 2022 to December 2024, and were randomly divided into the suppository group and the tablet group, 55 cases each. The tablet group using azithromycin, and the suppository group using vaginal suppositories on the basis of the tablet group. Comparison of the 2 groups efficacy, symptom disappearance time, pathogenic bacteria conversion rate, inflammation indicators, the incidence of adverse reactions, and changes in comfort score. Results: The total effective rate of the suppository group was 92.73% (51/55) higher than that of the tablet group 76.36% (42/55) (P < 0.05); the rate of pathogenic bacterial conversion in the suppository group was higher than that of the tablet group, and the time for disappearance of itching, disappearance of leukorrhea, disappearance of abnormal discharge, disappearance of dysuria, and disappearance of urinary pain and urgency in the suppository group was shorter than that of the tablet group (P < 0.05); compared with the tablet group, the post-treatment Tumor necrosis factor (TNF-α), interleukin 8 (IL-8), and C-reactive protein (CRP) levels were lower in the suppository group (P < 0.05); there was no significant difference in the incidence rate of adverse reactions in the suppository group of 3.64% (2/55) compared with that in the tablet group of 10.91% (6/55) (P > 0.05); and comfort scores were higher in the suppository group compared with the tablet group (P < 0.05 ). Conclusion: The synergistic therapy of azithromycin orally with topical vaginal administration is effective in nongonococcal cervicitis, which can improve the rate of pathogenic bacteria conversion, shorten the time of symptom disappearance, reduce the inflammatory reaction, and improve the comfort level.