Vitis vinifera var. L. País leaf extract, previously characterized, was microencapsulated by emulsion-solvent evaporation method using two different procedures: the conventional dropwise and micromixer device. The poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) was used as encapsulating polymer. In addition, the effect of extraction time and ethanol:water ratio on the yield and the content of bioactive compounds of grape leaf extract obtained by Soxhlet method was determined using the face-centered central composite design. The highest bioactive compound were obtained using a 70:30 ethanol:water solvent ratio during 4 cycles. This extract is mainly composed of cinnamic acid, quercetin-3-glucoside and quercetin-3-glucorinide, containing 3.56, 2.08 and 1.19 mg g−1 extract, respectively. The total polyphenol content determined by Folin Ciocalteu method was 164 ± 14 mg GAE g−1 extract. The microparticles (2–3 μm) had spherical shape with rough and porous surface. The encapsulation efficiency was 15.1% and 60.6% for the PHBV microparticles prepared using conventional dropwise and micromixer device, respectively. The antioxidant activity present in the original extract was preserved around 50%–80% and 20%–70% in the loaded microparticles. The best results were achieved when grape leaf extract was encapsulated using micromixer device. The cell viability assay in 3T3-L1 fibroblasts, showed that loaded microparticles are not cytotoxic. In conclusion micromixer device showed to be effective for the microencapsulation of grape leaf extract using PHBV as encapsuling polymer.