The aim of this study was the optimization of the gallic acid (GA) encapsulation efficiency within calcium alginate microparticles by the ionotropic gelation technique, using Box-Behnken design for the surface methodology response. For this purpose, three independent variables were selected: sodium alginate concentration (X1), calcium chloride concentration (X2), and gallic acid concentrations (X3). The influence of each variable on the encapsulation efficiency was evaluated. The optimum conditions to reach maximum encapsulation efficiency were found to be: X1 = 30 g/l (3%, w/v), X2 = 21.63 g/l (2.163%, w/v) and X3 = 15 g/l (1.5%, w/v), respectively. The encapsulation efficiency was determined to be 42.8%. The obtained microbeads were further examined using differential scanning calorimetry (DSC) and Fourier transform infrared (ATR-FTIR), and the inclusion of gallic acid was confirmed. The gallic acid concentration (X3) is the statistically significant factor in the optimization process. In addition, no autoxidation of the gallic acid compound was observed in the formulated calcium alginate microbeads. Scanning electron microscope (SEM) analysis showed that the shape of the particle was spherical for all formulations and their surface is wrinkled. The release study of the gallic acid carried out in an aqueous medium at pH value 6.8, showed that the GA release pattern was fast for all systems studied (85% at 20 min), and the profile of the release was influenced by the size of the calcium alginate microbeads. The obtained results reveal that the calcium alginate microbeads prepared through the ionotropic gelation technique possess great prominent for gallic acid encapsulation as well as its liberation.