The anti-diabetic effect of Cirsium setidens water extract and the combinations with Bletilla striata, Cymbidium kanran, and Sparganium stoloniferum Buch.-Ham. ethanolic extracts had been studied. The combination of four extracts (3:1:1:1) showed larger anti-diabetic activity in vitro and in vivo. It is notable that the single water extract from C. setidens exhibited more effective anti-diabetic effect than most of the combinations. We also investigated whether fermentation process was promoted the anti-diabetic activity. The data suggested the fermentation product of combination of four extracts (3:1:1:1) exhibited the strongest activity both in vitro and in vivo, which was higher than the non-fermented group. The result indicated the fermentation and the appropriate combination of extracts enhanced the anti-diabetes activity.