This study reports synthesis and antibacterial evaluation of the compounds derivatized from 3,4-dihalo-5-hydroxy-2(5H)-furanones. The minimum inhibitory concentration to planktonic bacteria and biofilm inhibition assays were used to evaluate their antibacterial functions. Three bacteria species (Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus) were used for evaluation. It was found that the bromine-containing derivatives were higher in antibacterial activity than their chlorine counterparts. The 5-position derivatization with two intact bromine or chlorine atoms attached showed a higher antibacterial activity than those derivatized at the 4-position. The derivatives with hydrophobic groups attached exhibited significantly higher antibacterial activities than those with hydrophilic ones attached. It was also found that the synthesized derivatives were more potent toward Pseudomonas aeruginosa than Escherichia coli and Staphylococcus aureus.