Background: The aim of this study was to evaluate the clinical efficacy of Xuanfei Baidu Decoction (XBD) combined with conventional drug therapy compared with conventional medicine alone in patients with coronavirus disease 2019 (COVID-19). Methods: Forty-two patients with COVID-19 were randomly assigned to XBD plus conventional medicine (n = 22) and conventional medicine alone (n = 20). Both groups were treated for 1 week. The primary endpoint was the disappearance rate of main symptoms (fever, cough, and fatigue). Results: Compared with the conventional medicine, the disappearance rate of clinical symptoms such as fever, cough, fatigue and loss of appetite in the experimental group were significantly reduced (P < 0.05). The number of white blood cells and lymphocytes in the experimental group increased significantly (P < 0.05), which all returned to normal parameters. Meanwhile, the C-reactive protein and erythrocyte sedimentation rate in the experimental group were significantly reduced (P < 0.05). Conclusion: XBD combined with conventional medicine may significantly improve patient's clinical symptoms, increase the number of white blood cells and lymphocytes to improve immunity, and also significantly reduce C-reactive protein and erythrocyte sedimentation rate to play an anti-inflammatory effect. However, it needs to be confirmed by a large sample study. Clinical trial registration: China Clinical Trial Registry (ChiCTR2000034795).