Protein is an essential food component, but it is also an allergen. This review discussed recent research about the impact of high-intensity ultrasound (HIU) on protein structure (primary, secondary, tertiary, and quaternary structure) and quality (allergenicity, physicochemical properties such as particle size, solubility and zeta potential, and functionality such as digestibility, antioxidant capacity, foaming and emulsifying properties). The corresponding mechanisms, advantages, limitations and future challenges are also discussed. HIU caused protein conformational alteration, protein unfolding, degradation and aggregation through cavitation effects, mechanical shear force, and free radical action. As a result, protein quality alteration was observed, including the reduction of allergenicity and particle size, the increase of solubility, digestibility, antioxidant capacity, foaming and emulsifying properties, and the alteration of zeta potential. The relationship between physicochemical properties and allergenicity as well as functionality was also observed. Future research focuses on the optimization of HIU conditions to balance allergenicity and functionality.