Chemical cross-linking provides an effective avenue to reduce the conformational entropy of polypeptide chains and hence has become a popular method to induce or force structural formation in peptides and proteins.Recently,other types of molecular constraints,especially photoresponsive linkers and functional groups,have also found increased use in a wide variety of applications.Herein,we provide a concise review of using various forms of molecular strategies to constrain proteins,thereby stabilizing their native states,gaining insight into their folding mechanisms,and/or providing a handle to trigger a conformational process of interest with light.The applications discussed here cover a wide range of topics,ranging from delineating the details of the protein folding energy landscape to controlling protein assembly and function. Chemical cross-linking provides an effective avenue to reduce the conformational entropy of polypeptide chains and hence has become a popular method to induce or force structural formation in peptides and proteins. Recently, other types of molecular constraints, especially photoresponsive linkers and functional groups, have also found increased use in a wide variety of applications. Herein, we provide a concise review of using various forms of molecular strategies to constrain proteins, thereby stabilizing their native states, gaining insight into their folding mechanisms, and / or providing a handle to trigger a conformational process of interest with light. The applications discussed here cover a wide range of topics, ranging from delineating the details of the protein folding energy landscape to controlling protein assembly and function.