Quantum chemical calculations and molecular dynamics simulations are carried out to study the host-guest inclusion complexes of cyclodextrins (alpha-, beta-, and gamma-CDs) with small guest molecules such as H2O, NH3, NH4+, C6H6, and bisimidazolyl compounds. The uptake ability of the CDs to accommodate the small molecules inside the cavity is examined by the sequential addition of 10 molecules of water or ammonia using the semiempirical (PM3) method. In the case of benzene, this was done up to six molecules, PM3 calculations indicate that alpha-, beta-, and gamma-CD can accommodate three, seven, and nine water molecules, respectively. In the case of NH3 as guest molecule, alpha-, beta-, and gamma-CDs can accommodate up to two, five, and six molecules, respectively. semiempirical calculations indicate that two benzene molecules can be accommodated in the alpha-CD cavity, whereas beta- and gamma-CD cavities adopt three and four benzene molecules, respectively. Molecular dynamics simulations were carried out for 1.0 its on benzene and bisimidazolyl complexes of CDs in explicit solvent (TIP3P water model). The interaction energies calculated by the MM/PBSA method reveal that ligand 1,6-bis(imidazol-1-yl) hexane (B) and 1,4-bis(imidizol-1-lylmethyl) benzene (C) molecules prefer to form 1:1 complexes with alpha-, beta-, and gamma-CDs. However, C preferentially forms 1:2 complexes with alpha-CDs. Ligands 1,10-bis(imidazol-1-lyl) decane (A) and 4,4'-(bis(imidazol-1-ylmethylene))biphenyl (D) form 1:2 complexes with alpha-, beta-, and gamma-CDs in head-to-head (HH) orientation of CDs. The stability of inclusion compounds depends oil the type of CD and the physicochemical properties of the involved guest. Both of these methods (semiempirical and MD simulations) reveal that beta-CDs form more stable complexes compared with alpha- and gamma-CDs with C, D, NH4+, and C6H6, whereas alpha-CD forms more stable complexes with A and B.