Quorum sensing (QS) regulated transcription factor SdiA responds to a broad range of AHLs and vitally involved in multiple gene expression. SdiA positively regulate the genes, responsible for MDR Salmonella typhi leads to serious potential public health problem. Aims of antimicrobial therapies are inhibiting cell growth (bacteriostatic) or causing cell death (bacteriocidal). Amongst these, therapies that promising strategies are development of challenging inhibitors against quorum sensing siganlling pathways causing multi drug resistant pathogens. In the present study, SdiA docked with inhibitors Coumarin-3-Carboxylic acid, Esculetin, Resveratrol, Ginkgolic acid, 7-Hydroxy indole, C6-HSL, Daphnetin, 4-Tetradecanol. The esculetin compound has the good G-score better binding affinity with SdiA. This study conclude Esculetin may potentially inhibit SdiA activity and their role in and MDR.