Thirteen compounds, based on benzofuran skeleton bearing aryl substituents at its C-3 position through methanone linker, were synthesized and screened for their antibacterial and antifungal activities against four bacteria Escherichia coli, Staphylococcus aureus, Methicillin-resistant S.aureus, Bacillus subtilis, and a fungus Candida albicans. Four hydrophobic benzofuran analogs were found to exhibit favorable antibacterial activities (MIC(80) = 0.39-3.12 μg/mL), which were better than the control drugs.