Previous studies indicate that the bioactive compounds of Eugenia stipitata pulp have antimutagenic, anticarcinogenic and antigenotoxic properties, but its use has been limited due to its high perishability. The aim of this study was to preserve bioactivity by using spray-drying microencapsulation, and is pioneering for its use of DSC to determine the best proportion of wall material (maltodextrin or gum arabic) and drying temperature (100 or 120 °C). The microparticles with maltodextrin (1:9)-100 °C had the best bioactivity conservation after in vitro gastrointestinal digestion, conserving 61% of total polyphenols, and 101%, 85% and 31% of antioxidant capacity according to the ABTS, FRAP and DPPH test methods respectively. These microparticles had a spherical morphology, presented good thermal stability and can be stored at a temperature range from 20 to 40 °C without becoming sticky. Therefore, spray-drying microencapsulation together with DSC is important for preserving a high concentration of bioactive compounds.