Salmonellosis is a common and widely distributed food borne disease where Salmonella typhimurium is one of the most important etiologic agents. The purpose of this study was to investigate the antimicrobial activity of Nymphaea tetragona alone and in combination with antibiotics against S. typhimurium. It also aimed to assess the plant for quorum sensing inhibition (QSI) activity and to identify the bioactive compounds. The antibacterial activities of the extract were assessed using broth microdilution method. Disk agar diffusion method was employed to determine the QSI and bioactive compounds were identified by GC-MS analysis. Ethyl acetate fraction of N. tetragona extract (EFNTE) demonstrated good antimicrobial activity (MIC 781 μg/mL) against 4 strains out of 5. FIC index ranged from 0.375 to 1.031 between EFNTE/tylosin and 0.515 to 1.250 between EFNTE/streptomycin against S. typhimurium. Among all extracts, EFNTE and butanol fraction more significantly inhibited pigment production of C. violaceum. Polyphenols were identified as major compound of EFNTE and butanol fraction. These results indicate that combination among N. tetragona extract and antibiotics could be useful to combat drug-resistance Salmonella infections and polyphenols are promising new components from N. tetragona that warrant further investigation as a candidate anti-Salmonella agent and quorum sensing inhibitor.