This contribution focused on the solubility improvement of the poorly water-soluble steroid hormone progesterone which, in its natural state, presents a reduced oral bioavailability. In the first part of this study, two simple, reproducible methods that were candidates for use in the preparation of inclusion complexes with cyclodextrins were investigated. Solubility capacities of the progesterone complex with hydroxypropyl-beta-CD (HPbeta-CD), hydoxypropyl-gamma-CD (HPgamma-CD), permethyl-beta-CD (PMbeta-CD), and sulfobutylether-beta-CD (SBEbeta-CD), prepared by the freeze-drying and precipitation methods, were evaluated by Higuchi phase solubility studies. The results showed that HPbeta-CD and PMbeta-CD were the most efficient among the four cyclodextrins for the solubilization of progesterone, with the highest apparent stability constants. Therefore, dissolution studies were conducted on these latest progesterone/cyclodextrin complexes and physical mixtures. Two additional natural cyclodextrins, beta-CD and gamma-CD, were taken as references. Hence, the influence of more highly soluble derivatives of beta-CD (HPbeta-CD, PMbeta-CD) on the progesterone dissolution rate, in comparison to pristine beta-CD, alongside an increase in the cavity width for gamma-CD versus beta-CD, were investigated. The dissolution kinetics of progesterone dissolved from HPbeta-CD, PMbeta-CD, and gamma-CD revealed higher constant rates in comparison to beta-CD. Therefore, the aim of the second part of this study was to investigate the possibility of improving the dissolution rate of progesterone/beta-CD binary systems upon formation of ternary complexes with the hydrophilic polymer, PEG 6000, as beta-CD had the smallest progesterone solubility and dissolution capacity among the four cyclodextrins studied (beta-CD, HPbeta-CD, HPgamma-CD and PMbeta-CD). The results indicated that dissolution constant rates were considerably enhanced for the 5% and 10% progesterone/beta-CD complexes in PEG 6000. The interaction of progesterone with the cyclodextrins of interest on the form of the binary physical mixtures, complexes, or ternary complexes were investigated by differential scanning calorimetry (DSC) and Fourier transformed-infrared spectroscopy (FT-IR). The results proved that progesterone was diffused into the cyclodextrin cavity, replacing the water molecules and, in case of ternary systems, that the progesterone beta-cyclodextrin was well dispersed into PEG, thus improving progesterone bioavailability for subsequent oral delivery in the same way as derivatized cyclodextrins. The present work proves that ternary complexes are promising systems for drug encapsulation.