The aim of this work was to obtain an inclusion complex between HP-β-CD and amiodarone in order to increase the solubility of this active agent. Drug−cyclodextrin interactions in solution were investigated using phase solubility studies. The Fourier transform infrared spectroscopy (FT-IR) spectra revealed the presence of the interactions between the components of the inclusion complex. Changes in crystallinity of the drug inside the inclusion complex were confirmed by X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). Thermogravimetric (TG) results demonstrated the modification of the drug thermal behavior due to the interactions with the host cyclodextrin. The dissolution rate of amiodarone from the inclusion complex was considerably increased as compared to dissolution of the pure drug. It has been established that the complexation of amiodarone with HP-β-CD offers the possibility to increase its aqueous solubility without the modification of its original structure.