Tissue engineering (TE) is one of the most challenging fields of research since it provides current alternative protocols and materials for the regeneration of damaged tissue. The success of TE has been mainly related to the right selection of nano-sized biocompatible materials for the development of matrixes, which can display excellent anatomical structure, functionality, mechanical properties, and histocompatibility. Today, the research community has paid particular attention to zein as a potential biomaterial for TE applications and nanotechnological approaches. Considering the properties of zein and the advances in the field, there is a need to reviewing the current state of the art of using this natural origin material for TE and nanotechnological applications. Therefore, the goal of this review paper is to elucidate the latest (over the last five years) applications and development works in the field, including TE, encapsulations of drugs, food, pesticides and bandaging for external wounds. In particular, attention has been focused on studies proving new breakthroughs and findings. Also, a complete background of zein’s properties and features are addressed.