A urethane-based polymer material, denoted HDI-1, was obtained from the addition reaction of beta-cyclodextrin (beta-CD) with 1,6-hexamethylene diisocyanate (HDI) at the 1:1 mole ratio. In aqueous solution and ambient temperature conditions, HDI-1 adopts a compact (coiled) morphology where the cross-linker units become coiled and are partially self-included in the annular hydroxyl (interstitial) region of beta-CD. As the temperature is raised or as p-nitrophenol (PNP) was included within the beta-CD cavity and the noninclusion sites of the polymer, an extended (uncoiled) morphology was adopted. The equilibrium distribution between the extended and the compact forms of HDI-1 is thermally and chemically switchable, in accordance with the hydration properties and host guest chemistry of this responsive polymer system. The molecular structure of this water-soluble urethane polymer and its host guest complexes with PNP were investigated using spectroscopic (Raman, H-1 NMR, induced circular dichroism), dynamic light scattering (DLS), and calorimetric (DSC) methods in aqueous solution at ambient pH, and compared with native beta-CD. This study reports on the unique supramolecular properties of a polymer that resembles a thermally and chemically responsive "molecular accordion".