This research aims to identify the polyphenolic metabolites, reported in ears and grains of Zea mays L. "purple corn" according to the current literature, with more significant interaction on HMG-CoA reductase, through in silico assays. Using the keyword combination "Zea mays L" AND "polyphenols" , a search was made in Google Scholar, PubMed, ScienceDirect and Scopus databases, identifying 22 polyphenolic compounds. Polyphenolic ligands and control molecules were prepared with the OpenBabel program and parameterized with AutoDock Tools. In addition, the crystallized structure of HMG-CoA reductase (1DQA) was downloaded from the Protein Data Bank database, then prepared in PyMOL and parameterized with AutoDock Tools. Molecular docking was performed in AutoDock Vina with a 100-time repetition for each ligand-target interaction. The results show that the hydrogen bonds with amino acids of importance in HMG-CoA reductase are ASN 658, ARG 590, and GLU 559. Protocatechuic acid, caffeic acid, vanillic acid, ferulic acid, p-coumaric acid, and 4-hydroxybenzoic acid presented lower affinity energy (ΔG°). The physicochemical and pharmacokinetic properties of the molecules with the best pharmacodynamic interaction were analyzed with the SwissADME and pkCSM servers, showing that protocatechuic, caffeic, vanillic, ferulic, p-coumaric and 4-hydroxybenzoic acids have the best physicochemical and pharmacokinetic profile. Therefore, this study gives us a clearer idea of the action of polyphenols on HMG-CoA reductase, which will allow obtaining new drug candidates for the treatment of hypercholesterolemia.