Hydrazone-type Schiff bases derived from natural compounds had demonstrate to be effective and versatile antioxidants. Particularly, the interest of this work is to analyze the antioxidant activity of cinnamaldehyde phenylhydrazone (CPH), an effective antioxidant synthesized by our group, through theoretical calculations. Considering that the enzymes cytochrome P450 (CP450) and NADPH oxidase (NO) are associated with the oxidative stress process, we chose these enzymes to evaluate their interaction with the antioxidant CPH. The interactions were analyzed by coupling studies performed with the SwissDock server. Considering the parameters of the scoring function based on the energy of the system, the best protein-ligand binding geometries were obtained and the interaction distances between the CPH enzymes were studied. Taking into account the information from all the data obtained, it could be concluded that CPH has strong interactions with enzymatic substrates due to electrostatic interactions with amino acid residues present in segments corresponding to hydrophobic domains. These results attest to the significant antioxidant capacity of CPH observed in experimental antioxidant tests.