Diabetes is still an incurable disease. To develop anti-diabetic medicine, we first evaluated the short term blood glucose-lowing effect of Bidens pilosa water extract in diabetes db/db mice. We found that a single oral dose of B. pilosa water extract significantly decreased blood glucose levels and increased serum insulin levels in db/db mice. Consistently, twenty-eight-day treatment with B. pilosa water extract showed that this extract could significantly lower postprandial blood glucose levels, increased blood insulin levels, improve glucose tolerance and decrease HbA1C level. This glucose-lowering effect seemed not to be related to food intake. Besides, B. pilosa water extract could protect pancreatic islet structure. We also tested insulin-secreting effects of B. pilosa water extract on rat β islets to secrete insulin as well as streptozocin-treated mice. We demonstrated that B. pilosa water extract could stimulate insulin release from pancreatic islets. However, this extract lost its ability to lower blood sugar levels in streptozocin-treated mice. Overall, our data showed that B. pilosa water extract treat type 2 diabetes in db/db mice via its regulation of insulin secretion. The B. pilsoa-based formulation has been commercialized locally for 12 years. Exland Biotechnology Inc. licensed the related patents in 2018 in an attempt to move this invention to clinical trial. Its licensing fee totals 76 million NT dollars.