An ethanolic extract of Artemisia dracunculus L. (PMI-5011) was shown to be hypoglycemic in animal models for Type 2 diabetes and contains at least 6 bioactive compounds responsible for its anti-diabetic properties. To evaluate the bioavailability of the active compounds, high fat dietary induced obese C57BL/6J male mice were gavaged with PMI-5011 at 500mg/kg body weight, after 4h of food restriction. Blood plasma samples (200uL) were obtained after ingestion, and the concentrations of the active compound in the blood sera were measured by electrospray LC-MS and determined to be maximal 4-6h after gavage. Formulations of the extract with bioenhancers/solubilizers were evaluated in vivo for hypoglycemic activity and their effect on the abundance of active compounds in blood sera. At doses of 50-500mg/kg/day, the hypoglycemic activity of the extract was enhanced 3-5-fold with the bioenhancer Labrasol, making it comparable to the activity of the anti-diabetic drug metformin. When combined with Labrasol, one of the active compounds, 2', 4'-dihydroxy-4-methoxydihydrochalcone, was at least as effective as metformin at doses of 200-300mg/kg/day. Therefore, bioenhancing agents like Labrasol can be used with multicomponent botanical therapeutics such as PMI-5011 to increase their efficacy and/or to reduce the effective dose.