In recent years, the rapid advancement of flexible sensors as the cornerstone of flexible electronics has propelled a flourishing evolution within the realm of flexible electronics. Unlike traditional flexible devices, hydrogel flexible sensors have characteristic advantages such as biocompatibility, adhesion, and adjustable mechanical properties and have similar properties to human skin. Especially, biobased hydrogels have become the preferred substrate material for flexible sensors due to increased environmental pressures caused by the scarcity of petrochemical resources. In this regard, proteins possess advantages such as diverse amino acid compositions, adjustable advanced structures, chemical modifiability, the application of protein engineering techniques, and the ability to respond to various external stimuli. These enable the hydrogels constructed from them to have greater designability, flexibility, and adaptability. As a result, their applications in manufacturing various types of sensors have experienced rapid growth. This work systematically reviews the sensing mechanism of protein-based hydrogels, focusing on the preparation of protein-based hydrogels and the optimization of flexible sensors mainly from the perspective of a typical type of animal-derived protein casein. In addition, while the potential of casein is recognized, the limitations of casein-based hydrogels in flexible sensor applications are explored, and insights are provided into the development trends of next-generation sensors based on casein-based hydrogel materials.