Calafate is a berry rich in anthocyanins that presents higher content of polyphenols than other fruits. Its compounds have been described previously, however, the potential thereof in preventing and treating degenerative disorders has not yet been studied. Due to its astringency, the consumption of this berry in its natural state is limited. To profit from the aforementioned properties and reduce palatability issues, calafate berry extracts were microencapsulated by spray drying, a rapid, cost-effective and scalable process, and were then compared with freeze drying as a control. The stability of its contents and its in-vitro potential, with respect to AChE activity and neuroprotection, were measured from the obtained microcapsules, resulting from temperature treatments and different encapsulant contents. The results indicated that the spray-dried powders were stable, despite high temperatures, and their encapsulation exhibited nearly 50% efficiency. The highest quantity of polyphenols and 3-O-glycosylated anthocyanins was obtained from encapsulation with 20% maltodextrin, at 120 °C. Temperature did not affect the microcapsules’ biological action, as demonstrated by their antioxidant activities. The prevention of Aβ peptide cytotoxicity in PC12 cells (20%) revealed that encapsulated calafate can confer neuroprotection. We conclude that spray-drying is an appropriate technique for scaling-up and producing new value-added calafate formulations with anti-neurodegenerative effects and vivid colors.