•New series of bis-thiazoles linked to 2-phenoxy-N-arylacetamide as novel hybrid molecules were designed and synthesized.•The isomeric bis(thiazoles) were prepared under similar reaction conditions by reacting the appropriate bis(thiosemicarbazone) with the corresponding α-haloketones.•All of the newly synthesized compounds were tested against four bacterial strains.•Compounds 8g and 8i have the most antibacterial activity against S. aureus and bacillus subtilis.•Molecular docking was performed to confirm the binding affinities of 8g and 8i. The reaction of the appropriate bis(α-haloketones) with the corresponding thiosemicarbazones in EtOH at reflux in the presence of a few drops of TEA produced good yields of novel bis-thiazoles linked to 2-phenoxy-N-arylacetamide as novel hybrid molecules. The isomeric bis(thiazoles) were prepared under similar reaction conditions by reacting the appropriate bis(thiosemicarbazone) with the corresponding α-haloketones. All of the newly synthesized compounds were tested against four bacterial strains. Compounds 8g and 8i have the most antibacterial activity against S. aureus and Bacillus subtilis. The molecular docking studies supported our findings, which demonstrated that compounds 8g and 8i could fit with favorable binding energies in the active sites of bacterial DNA gyrase B and thymidylate kinase, respectively. Display omitted