AbstractUrtica Dioica (UD) is a plant shown to reduce blood glucose levels upon oral ingestion; however, neither its active component nor its mechanism of action has been identified. One active fraction of this extract, termed UD‐1, was separated by molecular sieve column chromatography and purified by high performance liquid chromatography (HPLC). While UD‐1 did not stimulate insulin secretion in glucose‐responsive MIN6 clonal beta‐cells, chronic exposure (24 h) significantly enhanced glucose uptake (∼1.5‐fold) in L6‐GLUT4myc myoblast cells. Using HPLC and MALDI‐TOF, we further purified the UD‐1 fraction into two fractions termed UD‐1A and UD‐1B. Computational and structural analyses strongly suggested that the antidiabetic component of UD‐1 was due to one or more structurally related cyclical peptides that facilitate glucose uptake by forming unique glucose permeable pores. The structure and function of these glucose‐conducting pores are discussed herein. Copyright © 2009 John Wiley & Sons, Ltd.