The Jinwu Gutong (JWGT) capsule is a Chinese patent medicine that is widely used in the treatment of knee osteoarthritis (KOA) and osteoporosis in China and is considered to have the potential for good clinical efficacy.The purpose of this study was to systematically evaluate the clinical efficacy and safety of JWGT in the treatment of KOA.We searched the China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, PubMed, Embase and Cochrane Library databases to identify clinical trials that explore the use of JWGT only or JWGT combined with Western drugs (JWGT group) compared with the use of conventional Western drugs (Western drugs group) for the treatment of KOA. The clinical trials, that were retrieved from each database from the inception of the database to December 2021, were screened. We used the risk of bias assessment tool recommended by Cochrane to evaluate the quality of the included literature and RevMan 5.3 software for data analysis.A total of 17 clinical randomized controlled trials (RCTs) were included in this study, with a total of 1930 participants, including 1015 people in the experimental group and 915 people in the control group. The results of the meta-analysis showed that the JWGT group exhibited better efficacy than the Western drug group with respect to WOMAC score (WMD = -6.25, 95% CI = -8.09 to -4.41, P < 0.001), VAS score (WMD = -1.36, 95% CI = -2.17 to -0.55, P = 0.001), KSS score (WMD = 23.01, 95% CI = 21.42 to 24.59, P < 0.001), IL-6 (SMD = -3.30, 95% CI = -4.84 to -1.76, P < 0.001), TNF-α (SMD = -1.70, 95% CI = -2.02 to -1.38, P < 0.001). The effective rate (OR = 2.56, 95% CI = 1.83 to 3.57, P < 0.001) and incidence of adverse reactions was significantly lower in the JWGT group than in the control group (OR = 0.13, 95% CI = 0.07 to 0.21, P < 0.001). Subgroup analysis showed that JWGT + NSAIDs had more advantages in regard to efficacy (OR = 2.05, 95% CI = 1.35 to 3.12, P < 0.001), and reducing adverse reactions (OR = 0.10, 95% CI = 0.06 to 0.18, P < 0.001), VAS score (WMD = -1.00, 95% CI = -1.93 to -0.07, P = 0.04), KSS score (WMD = 17.39, 95% CI = 15.39 to 19.39, P < 0.001), WOMAC score (WMD = -2.84, 95% CI = -10.75 to 5.08, P < 0.001), IL-6 (SMD = -1.42, 95% CI = -2.08 to -0.75, P < 0.001) and TNF-α (SMD = -1.68, 95% CI = -1.93 to -1.43, P < 0.001) than NSAIDs alone. Compared with hyaluronic acid (HA) alone, JWGT + HA had better clinical efficacy (OR = 3.08, 95% CI = 1.48 to 6.40, P < 0.001). Compared with glucosamine (GS) alone, JWGT + GS significantly reduced the Lequesne index score (WMD = -0.53, 95% CI = -0.85 to -0.21, P = 0.001) and the serum TNF-α level (SMD = -1.68, 95% CI = -1.93 to -1.43, P < 0.001), but it had no significant advantage in reducing the serum IL-6 level (SMD = -4.53, 95% CI = -10.13 to 1.07, P = 0.11).JWGT is considered effective and safe in the treatment of KOA and is worthy of clinical application. In addition, the application of JWGT combined with NSAIDs, HA or GS can significantly improve the clinical efficacy of the latter agents in KOA treatment.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.