Bacterial quorum-sensing (QS) can cause bacterial biofilm formation, thus induce antibiotic resistance and inflammation in chronic bacterial infections. A series of novel 4-arylamidobenzyl substituted 5-bromomethylene-2(5H)-furanones were designed by introducing of brominated furanones into rosiglitazone skeleton, and their potential application in the treatment of chronic bacterial infection was evaluated with regard to their disruption of quorum sensing and anti-inflammatory activities in vitro as well as in animal infection model. Compound 2e displayed both potent QS inhibitory activity and anti-inflammatory activity. Further mechanism studies revealed that the biological effects of 2e and 2k could be attributed, at least in part, to their interaction with PPARγ, and consequent suppression of the activation of NF-κB and MAPK cascades. Importantly, pretreatment with 2e significantly protects mice from lethal-dose LPS challenge. Thus, these data suggest that the dual effective derivative 2e may serve as a valuable candidate for the treatment of chronic bacterial infection.