AIM: The aim of this study is to provide evidence of the effect of Duhuo Jisheng decoction (DHJSD) on knee osteoarthritis (KOA) of the cold-dampness obstruction syndrome type. METHODS: We searched PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Wanfang database, and the China Biology Medicine for randomized controlled trials (RCTs) evaluating DHJSD or DHJSD combined with other conventional therapies (DHJSD group) compared to conventional therapy (control group) for cold-dampness obstruction syndrome-type KOA. We calculated the pooled odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) using fixed- or random-effects models. RESULTS: Eleven RCTs, with a total of 895 patients, were included. The results showed that DHJSD could significantly improve the effective rate (OR = 3.13, 95%CI = 2.07 to 4.72, < 0.001), reduce both the WOMAC (MD = -12.06, 95%CI = -16.34 to -7.79, < 0.001) and VAS (MD = -1.02, 95%CI = -1.54 to -0.50, = 0.0001) scores, and reduce the serum IL-6 (MD = -0.80, 95%CI = -0.90 to -0.69, < 0.001) and TNF- (MD = -2.49, 95%CI = -2.77 to -2.21, < 0.001) levels during the treatment of cold-dampness obstruction syndrome-type KOA. The subgroup analysis showed that compared with glucosamine sulfate (GS) alone, DHJSD combined with GS significantly improved the effective rate (OR = 2.59, 95%CI = 1.19 to 5.65, = 0.02) and reduced the WOMAC (MD = -13.83, 95%CI = -16.14 to -11.51, < 0.001) and VAS (MD = -0.91, 95%CI = -1.27 to -0.55, < 0.001) scores. DHJSD + warm-needle acupuncture (WA) lowered the VAS score more than WA alone. There was no significant difference in the decrease in serum IL-1 between the DHJSD and control groups. CONCLUSION: This study shows that DHJSD can improve the clinical efficacy and reduce the VAS and WOMAC scores in the treatment of cold-dampness obstruction syndrome-type KOA. Compared with GS or WA alone, the combined application of DHJSD with GS or WA could better reduce both the VAS and WOMAC scores.