Glibenclamide is an antidiabetic drug showing low bioavailability as consequence of its low solubility. To solve this drawback, the interaction with cyclodextrins has been proposed. The formation of GB-βCDs inclusion complexes was carried out using different methods, βCD derivatives and drug-to-cyclodextrin ratios. The structures of the corresponding complexes have been studied by molecular modelling, X-ray diffraction and differential thermal analysis. The dissolution behavior of inclusion complexes has been compared to that of pure GB. Dimeric inclusion complexes were obtained with different CD disposals, head-to-head for βCD and head-to-tail for HPβCD and RMβCD. Amorphous inclusion complexes were obtained by employing methods of freeze-drying or coevaporation in ammonia-water. However, crystalline structures were formed by kneading and coevaporation in ethanol/water in the case of GB-βCD complexes. The arrangement of these structures depended on the GB:βCD ratio, yielding cage type structures for 1:3 and 1:5 ratios and channel-type structures for higher GB contents. The amount of GB released and its dissolution rate was considerably increased by the use of amorphous inclusion complexes; whereas, slower GB release rates were found from crystalline inclusion complexes formed by kneading or coevaporation in ethanol/water. In addition, it was found that the porous structure strongly conditioned the GB dissolution rate from crystalline products.