Abstract： Objective： To observe the clinical effect of Duhuo Jisheng Decoction combined with extracorporeal shock wave therapy （ESWT） in the treatment of knee osteoarthritis （KOA） and its impact on serum levels of cartilage oligomeric matrix protein （COMP） and matrix metalloproteinase-13 （MMP-13）. Methods：A total of 96 patients with KOA admitted to Ningbo Rehabilitation Hospital from January 2023 to December 2023 were selected and divided into an observation group and a control group using a random parallel grouping method，with 48 cases in each group. Two cases were excluded from each group， resulting in 46 cases completing the study in each group. The observation group was treated with Duhuo Jisheng Decoction combined with ESWT， and the control group received only ESWT. After four weeks of treatment， the clinical effects， traditional Chinese medicine syndrome scores， pain intensity [Visual Analogue Scale （VAS）]， and knee joint function [Western Ontario and McMaster Universities Osteoarthritis Index（ WOMAC）] were assessed；as well as serum COMP and MMP-13 levels. Results：The total effective rate in the observation group was 93.48% （43/46）， compared to 78.26% （36/46） in the control group， with significance in the difference between the two groups （P＜0.05）. After treatment， both groups showed a decrease in traditional Chinese medicine syndrome scores and VAS scores compared to before treatment （P＜0.05），and the two scores were lower in the observation group than in the control group （P＜0.05）. After treatment， the scores for pain， stiffness， and joint function in the WOMAC scale were decreased in the two groups compared to those before treatment （P＜0.05），and all scores were lower in the observation group than in the control group （P＜0.05）. After treatment， the levels of serum COMP and MMP-13 were decreased in the two groups compared to those before treatment （P＜0.05）， and both indicators were lower in the observation group than in the control group （P＜0.05）. Conclusion： Duhuo Jisheng Decoction combined with ESWT in the treatment of KOA can improve clinical effects， effectively alleviate traditional Chinese medicine syndromes， reduce knee joint pain， improve knee joint function， and downregulate serum COMP and MMP-13 levels.