Abstract: Zein is a primary by-product of corn starch processing, which is inexpensive and easily obtainable. Based on its unique self-assembly properties, zein could be constructed into nanoparticles through various methods, enabling the loading and delivery of bioactive substances. The preparation methods of nanoparticles include anti-solvent precipitation, pH-driven, electrospray, and microfluidics. The preparation methods can produce zein-based nanoparticles that respond to various environmental stimuli and exhibit stable properties. This article reviews recent advances in the preparation methods, response types, and application progress of stimulus-responsive zein-based nanoparticles. The nanoparticles respond to endogenous (pH, enzymes, and redox) and exogenous environmental stimuli (magnetic and light), which have been used for encapsulated delivery of bioactive substances in smart packaging of food, nanopesticides, and nanomedicine. However, maximizing the effect of active substances is difficult to achieve by relying only on a single stimulus-response. Therefore, nanoparticles responding to multiple stimuli (double stimulation, triple stimulation, etc.) have become a new development trend in the delivery field. In the future, more research should be invested in developing multi-stimulus responsive nanoparticles, and how to combine the multiple response properties of nanoparticles with the targeted delivery of nanoparticles remains to be further explored.