The new generation of designer solvents, such as deep eutectic solvents (DES), are generally claimed to be renewable and environmentally friendly. Nevertheless, this classification depends entirely on the nature of the selected components. The DES derived from choline chloride (ChCl) combined with a safe hydrogen?bond donor, such as urea, seemed ideal for the design of eco?friendly processes. In mixtures with water, it has been successfully used for lipase?catalyzed reactions of polar substrates. However, no studies have yet examined the role of the different components involved in these mixtures (ChCl, urea, and water) in the medium's functional properties, especially in the biocatalysis field where the enzymes are very sensitive to the environment. By analyzing the water activity (aw) and water content of the solvent, this paper reveals two different thermodynamic areas controlled by the strong association between ChCl and water. In addition, by varying the urea concentration, we show that urea has a denaturing effect on the enzyme and a positive effect on the selectivity of the reaction. Overall, this study made it possible to optimize the lipase?catalyzed alcoholysis reactions, with the synthesis of high yields of a wide range of lipophilic derivative compounds of phenolic acids.