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Encapsulation of bioactive molecules for therapeutic use is gaining great interest in the scientific community. Several encapsulation methodologies have been evaluated, sacrificing, in some cases, either encapsulation efficiency or compound integrity. Our work developed Maillard conjugates (MCs) based on the whey protein (WP)-Maltodextrin (MD) interaction to encapsulate quercetin by freeze-drying. The WP:MD ratio used (1:2 or 1:3) yielded the formation of MCs, demonstrated by an increased browning index and changes in the protein secondary structure. Freeze-drying showed high encapsulation efficiency, reaching 87.65% and 84.72% in treatments loaded with 3.3 mg quercetin/g MCs. Quercetin-loaded MCs showed spherical-shape (4-10 μm) and a negative charge, suggesting colloidal stability. Moreover, in vitro tests demonstrated a sustained release of quercetin throughout the oral, gastric, and intestinal phases, highlighting the MCs efficacy as bioactive delivery systems. This work provides useful information to design bioactive compound delivery systems for food and pharmaceutical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)