The knowledge of behavior of methyl-β-cyclodextrin (MβCD) in different solutions and thermodynamic aspects of complex host/guest formation with nimodipine (NMD) is essential in determining the best formulation in manifold fields of application. In the presented article, the behavior of MβCD in aqueous, mixed and alcoholic solutions was analyzed by using densimetric and acoustic methods within the temperature range of 288–313 K. Host/guest complex formation tendency between methyl-β-cyclodextrin and nimodipine was interpreted on the basis of thermodynamic parameters obtained from Isothermal Titration Calorimetry (ITC) in mixed media at 298 and 310 K. Obtained results reveal the tendency to aggregation of MβCD in water solutions and an inhibitory effect of ethanol on its course. The obtained results confirm the formation of a complex between MβCD and nimodipine of stoichiometric in a 1:1 ratio stabilized by nimodipine van der Waals forces. Complexation is spontaneous independently of temperature, driven mainly by hydrophobic forces.