Two novel quadruple hydrogen-bonded supramolecular structure 1:2 adducts of dimethylglyoxime-benzoic acid and dimethylglyoxime-cinnamic acid have been designed and optimized at the B3LYP/6-31G* level. The calculated results show that, at a temperature of 298.15 K and pressure of 0.1 MPa, the changes in the Gibbs free energy (DeltaG(T)) for the two aggregations from monomers to corresponding trimers are -41.7 and -42.7 kJ/mol, respectively, which imply that the processes of forming the trimers are spontaneous. Based on this design, we have synthesized the anticipatory supramolecular compounds successfully by selecting catalysts, and their crystal structures closely resemble the optimized structures. The predicted vibrational frequencies are in good agreement with the experimental values. Thermal stability analyses demonstrate that these two supramolecular compounds are new complexes and they are not the ordinary superposition of the original monomers.