This study aimed to determine the main active ingredients of the Ginseng-Gegen (Panax Ginseng-Radix Puerariae) drug pair, to predict relevant action targets, and to establish a network of "drug-active ingredients-targets", to ultimately explore the mechanism of Ginseng-Gegen in the treatment of mesenteric lymphadenitis.The Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform was used to screen the chemical constituents of Ginseng-Gegen, and the active ingredient targets were retrieved by UniProt database. The databases of GeneCards and the Online Mendelian Inheritance in Man (OMIM) were applied to search for mesenteric lymphadenitis-related targets. Cytoscape software was used to construct the network of active ingredient-action targets. The biological functions of the targets were analyzed in the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database.A total of 26 potential active ingredients of the Ginseng-Gegen drug pair were screened, with 128 drug-related targets and 255 mesenteric lymphadenitis-related targets. After matching, 23 potential targets were obtained for treating mesenteric lymphadenitis. Among them, MOL012297 (puerarin), MOL005344 (ginsenoside Rh2), and MOL000358 (beta-sitosterol) were linked to 3 or more key target genes. They were supposed to be important ingredients of Ginseng-Gegen in the treatment of mesenteric lymphadenitis.Ginseng-Gegen is related to oxidative stress and inflammation, and it is a part of the nuclear factor κB (NF-κB) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and the advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) signaling pathway. These biological processes and signaling pathways may be potential mechanisms of Ginseng-Gegen for treating mesenteric lymphadenitis.2022 Translational Pediatrics. All rights reserved.