The drying process used to obtain active food additives is critical to ensure its functionality. In this study, freeze- and spray-drying techniques were evaluated for encapsulation of extracts with antioxidant activity from yerba mate (Ilex paraguariensis), using maltodextrin (MD) as wall material. Additionally, the oxidative stability in a real food matrix (mayonnaise) was assessed. Both MD addition and drying methods affected the physical properties [moisture content, water activity (aW)] and oxidative stability. MD addition diminished moisture content and prevented polyphenol compounds from degradation. The spray-dried powders displayed the lowest moisture content (1.6 ± 0.3% bs), the highest polyphenol content (135.4 mg GAE/g pure extract), and oxidative stability than the freeze-dried samples. The antioxidant capacity of the encapsulated powder subjected to spray-drying increased the oxidative stability of the mayonnaise (258 ± 32 min) more than the other assayed system (165 ± 5 min). Therefore, a natural spray-dried antioxidant food additive was obtained with potential use in the food industry.