The recovery of byproducts from the food industry is a promising approach to obtain hydrophilic biopolymers with potential health benefits. In this work, the mucilage obtained from the peel of theOpuntia ficus-indica(OFI) fruit was compared with gum arabic (GA) as wall materials for the microencapsulation of Colombian blueberry anthocyanins, using the spray-drying process. For both types of microencapsulates, the following were determined: anthocyanin content (UV–vis and HPLC/MS-MS), total dietary content (enzymatic–gravimetric method), antioxidant activity (ORAC), color (CIELabparameters), morphology (SEM and particle size), and thermal behavior (DSC/TGA). Six different anthocyanins were identified by HPLC/MS-MS in the non-lyophilized Andean blueberry sample (LABP) and in the OFI-mucilage and GA microcapsules. OFI mucilage, compared to GA, favors the formation of larger spherical particles, a smoother surface without cracks, and greater thermal stability. The higher anthocyanin retention capacity in OFI microcapsules leads to higher antioxidant capacity and red coloration for this biomaterial. Consequently, the microencapsulation of anthocyanins with mucilage from the peel of the OFI fruit is proposed as a promising alternative for the protection and incorporation of this natural dye with high antioxidant capacity and dietary fiber content in new functional food/cosmetic formulations, while giving added value to the natural byproducts of OFI.