Protease inhibitors are regulatory proteins found in numerous animal tissues and fluids, plants, and microorganisms that reduce and inhibit the exacerbated and uncontrolled activity of the target proteases. Recently, novel biologic activities have been reported for plant protease inhibitors, including antimicrobial, and anticoagulants, thus pointing to possible Applications in and biotechnology. In this review, we provide a comparative overview of plant protease inhibitors classifying them into four groups according to their thermal and pH stability, then emphasizing the relevance of the physicochemical characteristics of these proteins for potential biotechnological and industrial Applications. Finally, we analyze the biological activities of the stable protease inhibitors previously characterized that are the most relevant to potential Applications in the food industry, and agriculture.