We investigated whether chemical modification potentiates anti-diabetic properties of ziyuglycoside on type 2 diabetes; our initial functional activity assay results showed that one week treatment of ZG02-ME, a deglycosylated and esterificated ZG01 derivative, more effectively decreased diabetic parameters such as blood glucose, glycated hemoglobin, and insulin levels than ZG01 treatment in db/db mice, indicating ZG02-ME has enhanced anti-diabetic activity in vivo. Here, INS is linked to type 2 diabetes mellitus.