This study evaluates the encapsulation of phytoactives from acerola (Malpighia emarginata) pomace extract (APE) into Saccharomyces cerevisiae cells via sonoprocessing coupled to spray drying (SPSD process). The effect of acoustic energy density (AED; 0–333.3 W/L), APE pH (3–11), and spray drying inlet temperature (T; 150–190 °C) on the encapsulation efficiency (EE) and yield (EY) of phenolic compounds and anthocyanins were investigated through a Box–Behnken experimental design (BBD). Results demonstrated that maximized EEs (> 63%) and EYs (> 126.7 mg/100 g) were obtained using the highest AED (333.3 W/L) and alkaline APE (pH 11), while the optimal T was set at 170 °C. Likewise, these process conditions also enhanced the antioxidant activity of biocapsules which positively correlated with the concentration of yeast encapsulated phytoactives by SPSD. Overall, our results demonstrate the versatility of SPSD protocol for manufacturing bioactive-enriched yeast biocapsules using complex mixtures of phytoactives. Further, it presents an innovative and sustainable roadmap for the management and repurposing of agri-food byproducts such as acerola pomace and other secondary streams of the food industry.