The present study was designed to assess the antimicrobial activity of 19 natural products belonging to terpenoids, alkaloids, thiophenes and phenolics against a panel of 14 Gram-negative multidrug-resistant (MDR) bacteria. The results demonstrated that amongst the studied compounds, alkaloids and terpenoids were less active contrary to flavonoids: neocyclomorusin (3) and candidone (6) and isoflavonoids: neobavaisoflavone (8) and daidzein (12). Thiophene, 2-(penta-1,3-diynyl)-5-(3,4-dihydroxybut-1-ynyl)thiophene (17) showed moderate and selective activities. Compounds 3, 6, 8 and 12 displayed minimal inhibitory concentration (MIC) ranged from 4 to 256 μg/mL on all the 14 tested bacteria. MIC values below 10 μg/mL were obtained with 8, 3, 6 and 12 against 50, 42.9, 35.7 and 21.4 % of the tested bacteria. The lowest MIC value of 4 μg/mL was obtained with compound 3 against Klebsiella pneumoniae ATCC11296, Enterobacter cloacae BM47, compound 6 against Escherichia coli ATCC8739, K. pneumoniae ATCC11296, E. cloacae BM47 and compound 8 against K. pneumoniae ATCC11296 and E. cloacae BM47. The activity of flavonoid 3 was better or equal to that of chloramphenicol in all tested K. pneumoniae, Providencia stuartii, E. aerogenes, E. cloacae and Pseudomonas aeruginosa strains. Within isoflavonoids, neobavaisoflavone scaffold was detected as a pharmacophoric moiety. This study indicates that natural products such as 3, 6 and 8 could be explored more to develop antimicrobial drugs to fight MDR bacterial infections.