The Mexican plum (Spondias purpurea L.) is a source of phenolic compounds; however, these compounds are susceptible to various factors (humidity, temperature, light, oxygen), as well as the digestion process, which can modify their bioaccessibility. This study aimed to extract and microencapsulate the phenolic compounds (PC), total anthocyanins (TA), ascorbic acid (AA), dehydroascorbic acid (DHA) and total vitamin C (AA+DHA) from Mexican plum ecotype “Cuernavaqueña” by spray drying (SD) and spout-fluid bed drying (SFB) and evaluate the bioaccessibility of these compounds by in vitro digestion. Optimal extraction conditions for bioactive compounds (BC) and antioxidant capacity (AC) were: three consecutive extractions at 40 °C, for 90 min each, with 1/5 solid-solvent ratio (4 g/20 mL), and 40% v/v aqueous ethanol. The extract without the encapsulation process suffered a significant (p ≤ 0.05) decrease in bioactive compounds and antioxidant capacity after in vitro digestion. Microcapsules obtained by SFB showed better retention and encapsulation efficiencies coupled with better protection against the digestion process. Microencapsulation by SFB protects the BC of Mexican plum, and it could be used in the food industry as ingredient to develop functional foods.