It is known that oxidative stress leads to aging and pathogenesis of many ailments. Antioxidants are considered to be one of the effective solutions for the oxidative stress and are used in the prevention and treatment of numerous diseases including inflammatory and infectious diseases, pre and post cancer therapy. In one of the authors' previous experimental study, potent antioxidant activities were observed from dendritic antioxidant (zero generation -G0) derived from syringaldehyde . In this study, we also designed its analogs derived from vanillin and 5-iodovanillin. The aim of our present study was to characterize and understand the molecular interaction of the dendritic antioxidants with pBR322 plasmid DNA using computer simulations, in the hope that only the chemical structures with promising results would be synthesized in the laboratory experiments for further investigation. Towards this undertaking, we investigated the effects of various non-covalent interactions of the dendritic antioxidants with double stranded (dsDNA) 20- and 80-base pairs of pBR322 and compared with those of commonly used small antioxidant molecules, like quercetin, and vitamins C. Molecular dynamics (MD) simulation has been adopted to generate binding site of the compound with pBR322 DNA after the conformational search. This study revealed that the nature of the diverse binding free energy components obtained via computational methodology. Based on interaction and binding energy, syringaldehyde-derivatized G0 dendrimer was found to be the most favorable entity for pBR322 DNA, followed by quercetin.