Objective To investigate the intervention effect of modified Duhuo Jisheng Decoction on knee osteoarthritis (KOA). Methods Eighty KOA patients were enrolled and randomly divided into two groups (40 cases each). The control group received oral glucosamine sulfate, while the observation group was additionally treated with modified Duhuo Jisheng Decoction. The treatment course lasted 12 weeks. Traditional Chinese medicine (TCM) syndrome scores, VAS, WOMAC scores, total effective rate, and adverse events were compared. Results The reduction in each score was significantly greater in the observation group than in the control group (P<0.05). The total effective rate in the observation group (92.50%) was higher than that in the control group (75.00%) (P<0.05). The incidence of adverse reactions in the observation group (5.00%) was lower than that in the control group (20.00%) (P<0.05). Conclusion Modified Duhuo Jisheng Decoction as an adjunctive treatment for KOA can effectively alleviate symptoms, promote joint function recovery, and has good safety.