Similar to mathematical chemistry, topology is at the very heart of systems biology. The rapidly increasing availability of protein structure data and network-based technologies allow insights into the biological function of proteins from topology. In this chapter, we summarized some network-based descriptors to study protein dynamics and allosteric regulation, including structure-based network descriptors and dynamic descriptors based on elastic network models. The applications of these network-based molecular descriptors in predicting functional sites and investigating allosteric regulation are illustrated by two case studies: DNMT1 and SARS-CoV-2 spike protein. We argued that network-based molecular descriptors prove to be a toolbox to study protein structures and dynamics, bridging the fields of mathematical chemistry and systems biology.