Traditional Chinese medicine (TCM) is a multi-component and multi-target agent and could treat complex diseases in a holistic way, especially infection diseases. However, the underlying pharmacology remains unclear. Fortunately, network pharmacology by integrating system biology and polypharmacology provides a strategy to address this issue. In this work, Reduning Injection (RDN), a well-used TCM treatment in the clinic for upper respiratory tract infections (URTIs), was investigated to interpret the molecular mechanism and predict new clinical directions by integrating molecular docking, network analysis and cell-based assays. 32 active ingredients and 38 potential targets were identified. In vitro experiments confirmed the bioactivities of the compounds against lipopolysaccharide (LPS)-stimulated PGE2 and NO production in RAW264.7 cells. Moreover, network analysis showed that RDN could not only inhibit viral replication but also alleviate the sickness symptoms of URTIs through directly targeting the key proteins in the respiratory viral life cycle and indirectly regulating host immune systems. In addition, other clinical applications of RDN such as neoplasms, cardiovascular diseases and immune system diseases were predicted on the basis of the relationships between targets and diseases.