The tunable property of ionic liquids (ILs) offers tremendous opportunity to rethink the strategy of current efforts to resolve technical challenges that occurred in many production approaches. To establish an efficient glycerolysis approach for enzymatic production of diglycerides (DG), this work reported a novel concept to improve DG yield by applying a binary IL system that consisted of one IL with better DG production selectivity and another IL being able to achieve higher conversion of triglycerides (TG). The candidates for combination were determined by individually examining lipase-catalyzed glycerolysis in different ILs, as a result, promising ones are divided into two groups based on their reaction specificities. The effects of parametric variables were then preliminarily evaluated, following a further investigation of the reaction performance in different binary IL systems from cross-group combinations. The combination of TOMA. Tf(2)N/Ammoeng 102 was employed for optimization by Response Surface Methodology. Eighty to eighty-five percent (mol%) of oil conversion and up to 90% (mol%) of total DG yield (73%, wt%) were obtained, which are markedly higher than those previously reported. This work demonstrated the practical feasibility to couple the technical advantage (high TG conversion and high DG production selective in this work) of individual ILs into a binary system to over-perform the reaction. It is believed that binary IL system could be also applicable to other enzymatic reaction systems for establishment of more efficient reaction protocols.