Objective: Shengjiang Powder (SJP) is a traditional Chinese medicine compound formula commonly used in the treatment of diabetic kidney disease (DKD). However, its material basis and mechanism of action are still unclear. Methods: In this study, the aqueous extract of SJP was obtained by aqueous decoction method, and the in vivo and in vitro constituents of SJP were analysed by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), and a network pharmacological strategy was established in conjunction with molecular docking in order to investigate the mechanism of action of SJP in the treatment of DKD. Results: The results identified 162 components, of which 28 could be absorbed into the blood and exert therapeutic effects in vivo. The main active ingredients were CT-1, CT-2, CT-7, BJC-2, and BJC-5, and the main targets in vivo were related to AKT1, MAPK1, MAPK3, MAPK8, and MAPK14, which could exert their therapeutic effects through the PI3K-Akt signaling pathway, Insulin resistance, and AGE-RAGE signaling pathway in diabetic complications, etc Conclusion: The present study adopts a comprehensive analytical strategy to reveal the pharmacodynamic material basis and mechanism of action of SJP in the treatment of DKD, and to provide a scientific basis for its clinical application.