β-Cyclodextrin (β-CD) was mixed with omeprazoleand some of its precursors in aqueous or water/ethanol solutions, and theresulting crystalline products have been characterized by elemental analysis,thermogravimetry, powder X-ray diffraction (XRD), FTIR and 13C CP MAS NMRspectroscopy. In the case of2-chloromethyl-4-methoxy-3,5-dimethylpyridine…HCl, itwas found that the solid product always consisted of pure β-CD hydrate. On the other hand, a 2 : 1(host-to-guest) inclusion complex was obtained between β-CD and2-methoxy-2-mercaptobenzimidazole. The thioether intermediate5-methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridine)methylthio]-1H-benzimidazoleand its sulfoxide derivative (omeprazole) both formed 1 : 1 inclusion complexes with β-CD. Powder XRD indicates that the crystal packing of β-CDhost molecules is herringbone-type for the 2 : 1 complex, and channel-typefor the 1 : 1 complexes. Ab initio calculations were carried out toinvestigate thehost–guest interactions. It was found that the interactionwith the pyridine fragment is wholly repulsive, due to the presence of severalring substituents. On the other hand, the inclusion of the benzimidazole fragmentis energetically favored, but highly dependent on the orientation of thesubstituent methoxy group.