Abstract: Objective To investigate the clinical effect of ultrasonic subgingival curettage combined with compound chlorhexidine in treatment of moderate and severe periodontitis. Methods Seventyeight patients with moderate and severe periodontitis were divided into observation group and control group, with 39 cases in each group. The control group was treated with ultrasonic subgingival curettage combined with aseptic distilled water, and the observation group was treated with ultrasonic subgingival curettage combined with compound chlorhexidine. Plaque index (PLI), bleeding index (BI), probing depth (PD), and attachment loss (AL) after 1 week and 6 weeks of treatment were compared between the two groups. The changes of prostaglandin E 2 (PGE 2) before treatment, 1week and 6 weeks after treatment were compared between the two groups. Results After 1 week of treatment, the levels of PLI, BI and PD in the anterior dental area of the observation group were significantly lower than those in the control group, and the levels of PLI, BI and AL in the posterior dental area were significantly lower than those in the control group(P<0.05). After 6 weeks of treatment, the levels of BI and PD in the anterior dental area of the observation group were significantly lower than those in the control group, and the levels of BI and AL in the posterior dental area were significantly lower than those in the control group (P<0.05). After 1week and 6 weeks of treatment, PGE 2 levels in the observation group were significantly lower than those in the control group(P<0.05). Conclusion Ultrasonic subgingival curettage combined with compound chlorhexidine in treatment of moderate and severe periodontitis has a significant effect, which can effectively reduce the level of PGE 2, alleviate the inflammatory response of periodontal tissues, and improve the oral health of patients.