Deep Eutectic Solvents have been specially designed, and used for the extraction of phenolics from olive tree (Olea europea) leaves. 11 deep eutectic solvents containing a hydrogen bond donor (glycerol, ethylene glycol, lactic acid, urea, dimethyl urea and D-sorbitol) and a hydrogen bond acceptor (L-proline, citric acid, glycerol, ethylimidazole and methylimidazole) with several molar ratios have been designed. Addition of water into the solvent system increased the extraction efficiency by a remarkable difference (45%). After the best combination has been decided to extract the primary phenolic (oleuropein), operation conditions (water content in the deep eutectic solvent, speed of the homogenizer and time for the extraction) of the homogenizer-aided extraction (HAEX) for olive leaf extract has been optimized through Box-Behnken design of Response Surface Approach. The experimental yields of oleuropein, verbascoside and rutin were 15.50, 5.51 and 0.98 mg per gram dried leaf under the optimal conditions (48.9% of water in DES for 60 sec at 13310 rpm). Our best DES (citric acid/lactic acid) has yielded the most efficient extract rich in oleuropein, even with an approximate to 8% higher performance than that of a most commonly used solvent (75% ethanol).
