Gyejibokryeong-hwan (GBH) is a traditional formula comprised of five herbal medicines that is frequently used to treat blood stasis and related complex multifactorial disorders such as atherosclerosis. The present study used network pharmacology and molecular docking simulations to clarify the effect and mechanism of the components of GBH. Active compounds were selected using Oriental Medicine Advanced Searching Integrated System (OASIS) and the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and target genes linked to the selected components were retrieved using Search Tool for Interacting Chemicals (STITCH) and GeneCards. Functional analysis of potential target genes was performed through the Annotation, Visualization and Integrated Discovery (DAVID) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and molecular docking confirmed the correlation between five core compounds (quercetin, kaempferol, baicalein, ellagic acid, and baicalin) and six potential target genes (AKT1, CASP3, MAPK1, MAPK3, NOS2, and PTGS2). Molecular docking studies indicated that quercetin strongly interacted with six potential target proteins. Thus, these potential target proteins were closely related to TNF, HIF-1, FoxO, and PI3K-Akt signal pathways, suggesting that these factors and pathways may mediate the beneficial effects of GBH on atherosclerosis. Our results identify target genes and pathways that may mediate the clinical effects of the compounds contained within GBH on atherosclerosis.