Objectives: In order to better understand the synergetic activities of radix aconite lateralis praeparata (Fuzi)-rheum officinale (Dahuang) herb pairs. Material and methods: The target proteins of Fuzi and Dahuang were retrieved from PubChem database and were uploaded to ingenuity pathway analysis (IPA) platform. Then we carried out molecular network analysis and canonical pathway analysis. Finally, we found out specific molecules, networks and pathways, which embodied the synergetic activities of Fuzi-Dahuang herb pairs. Results: 5 target proteins in Fuzi and 44 target proteins in Dahuang were retrieved from PubChem database. Ubiquitin C (UBC) is a shared molecule in Fuzi network and Dahuang network. Bio-functions of Fuzi and Dahuang involved in gastrointestinal disease, cardiovascular disease, endocrine system disorders, inflammatory disease, as well as renal and urological disease, etc. 14-3-3 mediated signaling is the pathway related with tubulin and tau that are from Fuzi and Dahuang target proteins respectively. Conclusions: Regulating UBC and 14-3-3 mediated signaling pathway might partly decipher the synergetic biological activities of Fuzi-Dahuang herb pairs. Network pharmacology approaches contribute to find the biological activities of herb pairs fully. This study provides a new paradigm for better understanding the synergy mechanism of the compatibility of herb pairs.