SummaryThe aim of this study was to develop and evaluate the bioactive properties and storage stability of microcapsules (MCs) obtained by co‐encapsulation of the potential probiotic yeast Kluyveromyces marxianus VM004 and peanut skin polyphenolic extract (PSE) by spray drying, using whey protein concentrate (WPC) and water‐soluble chitosan (WSCh) as wall materials. The results showed that the selected wall materials provided protection to yeast during spray drying, storage, and simulated gastrointestinal conditions, obtaining better results for WPC and higher concentrations of PSE. Moreover, all formulations demonstrated cytoprotective effects against menadione‐induced oxidative stress in normal rat ileum epithelial cells (IEC‐18) at all concentrations and storage temperatures evaluated. These results suggest that the obtained MCs could be potential functional food ingredients, considering their antioxidant, cytoprotective, and potential probiotic properties.