The goal of this work was to select the best combination of encapsulants for the microencapsulation of oregano essential oil by spray dryer with the addition of Arabic gum (AG), modified starch (MS) and maltodextrin (MA). The simplex-centroid method was used to obtain an optimal objective function with three variables. Analytical methods for carvacrol quantification, water activity, moisture content, wettability, solubility, encapsulation efficiency (ME) and oil retention (RT) were used to evaluate the best combination of encapsulants. The use of AG as a single wall material increased ME up to 93%. Carvacrol is the major phenolic compound existent in the oregano essential oil. Carvacrol exhibits a maximum concentration of 57.8% in the microparticle with the use of 62.5% AG and 37.5% MA. A greater RT (77.39%) was obtained when 74.5% AG; MS 12.7% and 12.7% MA were applied, and ME (93%) was improved with 100% of gum.