Cyclodextrins' unique molecular structure with hydrophilic exterior surface and nonpolar cavity interior is responsible for their specific complexation properties. Although a wealth of information about these molecules has been accumulated, many aspects of their coordination chemistry remain unknown. For example, there are no systematic studies on the key factors controlling the processes of metal binding and selectivity in these systems. In the computational study herein, DFT molecular modeling has been employed to study the interactions of either hydrated or nonhydrated IIA/IIB group metal cations (Be2+, Mg2+, Ca2+, Sr2+, Ba2+, Zn2+, Cd2+, Hg2+) with the host a-cyclodextrin molecules. The thermodynamic descriptors (Gibbs free energies in the gas phase and in water medium) of the metal binding to alpha-cyclodextrin have been evaluated, and the effect of various factors (metal's radius, electron configuration and coordination number, and host molecule flexibility and binding site locality) on the interactions between the two binding partners has been assessed. The results obtained shed light on the intimate mechanism of the metal binding to a-cyclodextrin and disclose the key factors governing the process.