In this study, we designed, synthesized, and characterized twenty-two new thiazole hybrids with 2,4,6-trifluorobenzene and 6-bromo-2,3-difluorobenzene moieties.The design of the target mols. is based on the mol. hybridization approach.The structures of intermediates and thiazole hybrids were elucidated by 1H NMR, 13C NMR, HRMS, 19F-NMR, and FTIR spectroscopic techniques.The inhibitory efficacy of the synthesized compounds was assessed against strains of S. pyogenes, S. aureus, P. aeruginosa, Escherichia coli, A. niger, and C. albicans, expressed in terms of MIC values.Compounds hydrogen, 4-bromo, 4-Me, 4-cyano, 4-Ph groups containing trifluorobenzene phenylthiazole and 4-fluoro, 4-Me, Ph groups containing difluorobenzene phenylthiazole showed substantial antibacterial effectiveness against several tested bacterial strains, exhibiting the MIC value of 62.5μg/mL, compared to typical antibacterial medications such as ciprofloxacin (MIC = 50μg/mL) and chloramphenicol (MIC = 50μg/mL).Compounds difluorobenzylidene hydrazinecarbothioamide, 4-hydroxy, 4-Ph groups containing trifluorobenzene phenylthiazole and 4-Ph groups containing difluorobenzene phenylthiazole outperformed griseofulvin, a standard antifungal drug, with an MFC value of 250μg/mL against C. albicans.The in-silico anal. of the highly potent antibacterial compounds 4-bromo, 4-hydroxy, 4-Ph groups containing trifluorobenzene phenylthiazole against S. aureus DNA gyrase (PDB: 2xct) revealed that these compounds formed reasonably stable complexes with DNA gyrase, exhibiting binding affinities of -9.7, -9.6, -9.8, and -9.6 kcal/mol, resp.In this way, both, docking anal. and antimicrobial activities suggest 4-bromo, 4-hydroxy, 4-Ph groups containing trifluorobenzene phenylthiazole and 4-fluoro group containing difluorobenzene phenylthiazole to possess antibacterial activities probably through binding to S. aureus DNA gyrase.These compounds need to be further explored to unravel their antibacterial potentials.