New approaches for oral administration of insulin are strongly related to novel insulin carriers. The aim of this study was the insulin microencapsulation in a new zinc-silica matrix for drug protection and controlled release. Zinc-silica microparticles loaded with insulin were obtained by sol-gel process via spray drying and freeze drying methods. Inorganic silica matrix isolates and constrains the movement of the biomolecules preventing their aggregation and denaturation, while the zinc oxide improves the system stability. Moreover, formation of insulin hexamers in the presence of zinc ions leads to an increased stability of the insulin three-dimensional structure during preparation, storage and release. The particles were characterized with respect to average size, specific surface area, porosity and morphology. In vitro behavior of insulin-loaded particles together with protein structural conformation was also evaluated. The release profile can be adapted by synthesis route of microparticles.