Thiazole derivatives are potential candidates for drug development. They can be efficiently synthesized and are extremely active against several diseases, including antimicrobial screening. A series of 2-(2-(3-methoxy-4-(prop-2-yn-1-yloxy)benzylidene)hydrazinyl)-4-(p-tolyl)-4,5-dihydrothiazole (5a-f) and 2-((2-(4-(4-bromophenyl)-thiazol-2-yl)hydrazono)methyl)-5-(diethylamino)phenol (8g-j). The synthesized compounds’ have been characterized by spectral analysis, such as mass, FT-IR, 1H & 13C NMR. All the synthesized compounds were screened for in vitro antibacterial activity against some Gram-positive (Staphylococcus aureus, Streptococcus pyogenes) and Gram-negative (Escherichia coli, Klebsila) bacteria. The thiazole derivatives with a pharmacologically potent group provide the valued therapeutic involvement in the treatment of microbial diseases, especially against bacterial and fungal infections. Furthermore, to gauze their plausible mechanism of action and thermodynamic interaction governing these molecules’ binding, a molecular docking study was carried out against crucial target bacterial DNA, Gyrase.