Bio-based solvents have recently been discussed as sustainable green and promising alternatives to conventional organic media for enzymatic processes. In this paper, highly regioselective synthesis of the 6aEuro(3)-O-crotonyl-polydatin catalyzed by Thermomyces lanuginosus lipase (TLL) in biomass-derived 2-methyltetrahydrofuran (2-MeTHF) was successfully performed for the first time. The results indicated that TLL lipase displayed significantly improved catalytic performance in 2-MeTHF than in other traditional solvents. Under the optimal conditions, the initial reaction rate, 6aEuro(3)-regioselectivity, and maximum substrate conversion were as high as 12.38 mM h(-1), 100 %, and 100 %, respectively. Moreover, further investigations on the operational stability, kinetic parameters like V (max), K (m), V (max)/K (m), and E (a) revealed that 2-MeTHF exhibited excellent biocompatibility and rendered the greener process of the enzymatic acylation.