Zein is a natural, biocompatible, and biodegradable polymer widely used in the pharmaceutical, biomedical, and packaging fields because of its low water vapor permeability, antibacterial activity, and hydrophobicity. It is a vegetal protein extracted from renewable resources (it is the major storage protein from corn). There has been growing attention to producing zein-based drug delivery systems in the recent years. Being a hydrophobic biopolymer, it is used in the controlled and targeted delivery of active principles. This review examines the present-day landscape of zein-based microparticles and nanoparticles, focusing on the different techniques used to obtain particles, the optimization of process parameters, advantages, disadvantages, and final applications.