Background: Benzoxazole has grown significantly in the domain of medicine owing to the large spectrum of pharmacological actions that heterocycles exhibit.One of the greatest problems confronting public health current century is antibiotic resistance thus driving up the need for antimicrobial medication is necessary. As tetrahydrofolate oversees transferring mono-carbon residues to produce nucleotides and amino acids, the Dihydrofolate reductase receptor (DHFR) is a crucial impetus in the metabolism of DNA and amino acids. Method: The dihydrofolate reductase receptor (PDB ID: 3SRW and Resolution 1.70Å) was the target of molecular docking investigations for a series of reduced Schiff base derivatives containing benzoxazole.For this,softwares used arePyRx, Pymol, and Discovery studio visualizer. For the pharmacokinetics studies, BOILED Egg visuals, toxicity, and bioactivity were studiedby Swiss ADME, PreADMET, PkCSM, ADMETSAR, and Molinspiration respectively. Result: ReducedSchiff base designedderivatives showeda superior binding affinity between -9.9 to -10.9 kcal/mol whereas referenced drug ciprofloxacin based on broad-spectrum antibioticshowedtightbinding affinity of - 7.5kcal/mol and Boxazomycinat -8.8 kcal/mol.THR X:47, GLY X: 95, THR X: 97, ASN X: 19, and LEU X:63 is some of the amino acids that interact at the protein site via conventional hydrogen bonding.The physicochemical parameters showed that each of the recommended compounds had good synthetic effectiveness and do not break Lipinski's rule of five.Furthermore, Boiled egg visuals demonstrated an elevated score of being absorbed by the mammalian Intestinal tract and perhaps reaching the nervous system. Whereas, all designed compound revels applicable toxicology properties and shows moderate bioactivity. Conclusion: Inconclusion, all the designed compounds have demonstrated outstanding pharmacokinetic characteristics and good bioavailability characteristics optimized as novel antimicrobial medications.