Acute hepatopancreatic necrosis disease (AHPND), caused by V. parahaemolyticus PirAvp/PirBvp toxins, is a significant threat to the shrimp farming industry. We successfully formulated an essential oil blend against it. The ProteinPlus and ezPocet binding site modeling revealed that the ligand-binding pockets of the toxins are possibly located on the central part of the protein and play an essential role in the small molecule ligand interaction cellular target receptors binding. To gain further insights into the interactions present at the ligand-toxins interface, each of the selected molecules in essential oil blend formulation (EOBF) was docked into V. parahaemolyticus PirAvp/PirBvp toxins protein using AutoDock Vina. Selected molecules in EOBF composition are first voxelized into 8 different pharmacophoric-like features. After that, they have been used as input for a DCNN model. AutoDock Vina molecular docking results for the selected molecules from EOBF were visualized and analyzed by PyMol and Discovery Studio software. We set the EOBF components to identify V. parahaemolyticus PirAvp/PirBvp toxins potential inhibitors in EOBF using a structure-based virtual screening approach and molecular docking, based on the quantitative composition and biological activity data. A total of 15 molecules were selected for molecular docking into V. parahaemolyticus PirAvp/PirBvp toxins. These 15 EOBF molecules interacted with amino acid residues located on C-terminal alpha-helixes and the central part of the beta-strands of Cry domains II and III of the B. thuringiensis Cry toxin Po-1 Cry ligand-binding pocket with high druggability (Figure). All of these EOBF molecules interacted with key amino acid residues responsible for PirBvp/PirBvp homodimers formation. Moreover, all the EOBF compounds (except anethole) can disturb and prevent the PirBvp/PirAvp heterotetramer structure. Thus, 6 EOBF compounds could be potent suppressors of 3 primary potential pathogenic mechanisms of V. parahaemolyticus–induced AHPND in P. vannamei. All the rest 9 EOBF compounds could be potent inhibitors of 2 primary possible pathogenic mechanisms of V. parahaemolyticus–induced AHPND in shrimps.