Oligodimethylsiloxanes (ODMSs) containing a beta-D-glucopyranosyl group at one chain end (Glc-ODMSs) with various molecular weights were prepared to develop a silicone-based polymeric transdermal penetration enhancer with a non-ionic polar end group. Glc-ODMSs were prepared by hydrosilylation of hydrosilyl-terminated ODMS with 1-allyl-beta-D-glucose tetraacetate in the presence of bis(benzonitrile)platinum dichloride as the catalyst, followed by hydrolysis of the acetyl groups with sodium methoxide. The enhancing effect in the drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Antipyrine was used as a model drug, and the amount of drug permeating through the rat abdominal skin with or without Glc-ODMS was determined by HPLC. These enhancers were effective for the penetration of antipyrine. On the other hand, the enhancing effects were influenced by the concentration of Glc-ODMS coexisted regardless of its ODMS chain length. The enhancing effect was also observed by the pretreatment of the skin with Glc-ODMS before the drug permeation, the results of which suggested that the induction periods to appear the enhancing effects were different between Glc-ODMSs with the short and the long ODMS chain lengths. Furthermore, according to the Draize test, Glc-ODMSs exhibited no irritation to the skin regardless of the ODMS chain length.