How thermostability and gelation of globular protein are affected by cosolvent systems present in food systems is critical to understanding their functionality. The expression of these functional attributes depends on the molecular structure and thermal-mechanical history of the protein, as well as its chemical environment. To improve the design of processing protein-containing food systems, one must fully understand the thermodynamic, kinetic, and structural impact of cosolvent on globular protein gelation. This review focuses on the impact of weakly interacting neutral cosolvent systems (for example, sugars and polyols) on the gelation of globular proteins. The physicochemical mechanisms by which these cosolvent systems can modulate protein gelation are highlighted from a thermodynamic, kinetic, and structural point of view.