Zhizi Baipi decoction is a classic traditional Chinese medicine formula for the treatment of jaundice and various liver diseases. The chemical components of Zhizi baipi decoction were not clear resulting of the paucity of relevant studies, which hindered the elucidation of the pharmacological mechanism, and the comprehensive development and utilization of Zhizi baipi decoction in clinical. In this study, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry combined with the UNIFI natural product information analysis platform was used to rapidly analyze and identify the chemical components in Zhizi baipi decoction. A total of 122 chemical components, including 53 flavonoids, 16 alkaloids, 25 terpenoids, five phenylpropanoids, 14 organic acids, and seven others, were identified from Zhizi baipi decoction. These compounds may be the active components of Zhizi baipi decoction. The method established in this study can systematically, rapidly, and accurately resolve the chemical components in Zhizi baipi decoction, which lays the foundation for further establishment of the pharmacodynamic substance basis and quality control of Zhizi baipi decoction. © 2022 Wiley-VCH GmbH.