The inspection of molecular interaction widespread in allopurinol and in aqueous solutions of α-, β- and HP-β-cyclodextrin have been probed by thermophysical properties. The established complexes obtained with 1:1 stoichiometry. Role of solvent (aqueous solution of α-CD, β-CD, HP-β-CD) and contribution of solute–solute and solute–solvent interactions to solution complexes, have also been analyzed via stability constant-NMR, UV, steady state fluorescence, FTIR, HRMS, SEM, PXRD, cytotoxicity, hydrophobic effect, hydrogen-bonding, structural effects in creation of inclusion complexes.