>Magister Scientiae - MSc / Extracts from the root bark, stem bark, and leaves of R. natalensis were screened for antibacterial activity against standard bacterial strains; Staphylococcus aureas, Escherichia coli and Pseudomonas aureginosa, and fungi; Candida albicans, Trichophyton mentagrophytes or Microsporum gyseum. Chromatographic techniques were utilized to isolate pure compounds. This study validates and documents, in a systematic way, the antimicrobial properties of the R.natalensis used for many years by many people of the world. It also provides valuable information for further phytochemical isolation and characterization studies of active compounds, necessary for the development of new drugs. The extractions were carried out using broad spectrum of solvents (hexane, dichloromethane, ethyl acetate, and methanol).Fractionation was done using standard chromatographic techniques. A total of seven (7)compounds were isolated from R. natalensis. Three of the isolates were characterized and their structures were unambiguously established by detailed spectroscopic analysis that involved high resolution mass spectrometry, 1D and 2D-NMR spectral data experiments 1H, 13C, DEPT,COSY, HMBC, and NOESY. These compounds are: 3-(1-(2,4-dihydroxyphenyl)-3,3-bis(4- hydroxyphenyl)-1-oxopropan-2-yl)-7-methoxy-4H-chromone-4-one (39), Rhuschromone, a novel compound isolated for the first time, 2’,4’ dihydroxychalcone-(4-O-5’’’)-4’’,2’’’,4’’’-trihydroxychalcone (40) and 3-((Z)-heptadec-13-enyl) benzene-1,2-diol (41), an urushiol.Compound 39 recorded the highest activity zone of inhibition (21mm) against S. aureas, which was found to be 50% as active the chloramphenicol standard used. The traditional use of the extracts in infections and inflammatory conditions is rationalized based on the content of the isolated compounds, and it has been proposed that the total crude extract, with its contents of so many bioactive compounds, could be formulated for use in many infections, microbial or fungal.Furthermore, not all of the species studied to date have been fully characterized for potential bioactivities. Thus, there remains a significant research gap spanning the range from lead chemical discovery through process development and optimization in order to better understand the full bioactive potential of many of these plants.