The current study aimed to explore the mechanism of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis based on the combination of Vanquish Ultra High Performance Liquid Chromatography Q Exactive IV Pole-electrostatic field orbital trap high resolution mass spectrometer (UHPLC-Q-Orbitrap HRMS) and network pharmacology. Firstly, UHPLC-Q-Orbitrap HRMS was established and applied to separation and identification of the chemical com-ponents of GSZD. Then, using network pharmacology analysis to obtain the potential active com-ponents and candidate targets underlying the effect of GSZD on gouty arthritis (GA). Through targeted and untargeted analysis, a total of 79 components, including 3 chromones, 26 flavonoids, 10 alkaloids, 10 phenolic acids, 7 nucleosides and nucleobases, and 23 other components, were char-acterized from GSZD. 11 compounds were considered to potentially key active compounds against GA which may be via interacting with multiple inflammatory factors and multiple inflammatory pathways.(c) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).