To investigate the effective components and underlying mechanism of Paeoniae radix rubra (PRR) in treating sepsis-induced coagulopathy (SIC) on the basis of network pharmacology and molecular docking approaches. At present, no therapeutic agent has been approved for the treatment of SIC. Identifying drugs for SIC from Chinese medicine is an encouraging research direction. The predicted targets and effective components of PRR were identified by analysis of the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Bio-informatics databases were employed to identify the disease targets of SIC. These key targets were then uploaded to the STRING database to generate protein–protein interaction networks. The ORG package in rv4.1.2 software was applied for functional and pathway enrichment analyses of the key targets. Finally, discovery studio software was used to perform docking analyses of key targets and effective components. Nine chemically active components and 84 common targets associated with drugs and SIC were identified. Protein–protein interaction (PPI) network analysis identified several key targets. Further analysis identified enrichment in several signaling pathways; these changes could exert influence on a number of biological processes, including responses to xenobiotic stimuli, oxidative stress, molecules of bacterial origin, thus playing an anti-SIC pharmacological role. According to molecular docking results, these key targets had strong binding affinity to the active components. PRR can contribute to SIC by medicating core target genes (e.g., CASP3, PTGS2, TP53, AKT1, MMP9, TNF, JUN, IL6, and CXCL8), and regulating multiple key pathways (e.g., the lipid and atherosclerosis pathway).