Pushed by the environmental pollution and health hazards of plastic packaging, the development of biodegradable food packaging films (FPFs) is a necessary and sustainable trend for social development. Most protein molecules have excellent film-forming properties as natural polymer matrices, and the assembled films have excellent barrier properties, but show defects such as low water resistance and poor mechanical properties. In order to improve the performance of protein-based films, transglutaminase (TG) is used as a safe and green cross-linking (CL) agent. This work covers recent developments on TG cross-linked protein-based FPFs, mainly comprising proteins of animal and plant origin, including gelatin, whey protein, zein, soy proteins, bitter vetch protein, etc. The chemical properties and reaction mechanism of TG are briefly introduced, focusing on the effects of TG CL on the physicochemical properties of different protein-based FPFs, including barrier properties, water resistance, mechanical properties and thermal stability. It is concluded that the addition of TG can significantly improve the physical and mechanical properties of protein-based films, mainly improving their water resistance, barrier, mechanical and thermal properties. It is worth noting that the effect of TG on the properties of protein-based films is not only related to the concentration of TG added, but also related to CL temperature and other factors. Moreover, TG can also be used in combination with other strategies to improve the properties of protein-based films.