This study was aimed at determining the antibacterial activities of Andrographis paniculata on methicillin and vancomycin resistant enteric bacteria isolated from River Owena, Owena, Nigeria. Water samples were collected weekly from River Owena over a period of six weeks (n = 6). The bacteriological evaluation of the water samples was carried out using standard microbiological method. A. paniculata leaf and stem extracts were prepared using the polar (i.e., methanol) and nonpolar (i.e., n-hexane) solvents. The phytochemical constituents and antibacterial activity of all the extracts of A. paniculata leaf and stem were investigated using standard methods. Results revealed that methanol extracts from A. paniculata contained the maximum amount of phytochemicals when compared to that of the n- hexane extracts. Salmonella and Shigella were both resistant to vancomycin, while they were only susceptible to methicillin once throughout the sampling week. The methanol extracts from A. paniculata showed higher antibacterial activity against the targeted bacterial isolates of enteric origin which include E. coli, faecal coliforms, Shigella, Salmonella and intestinal enterococci. The methanol leaf extract of A. paniculata showed the maximum antibacterial activity against E. coli, Salmonella, Shigella, intestinal enterococci and faecal coliform with zones of inhibition 29.0 mm, 26.00 mm, 21.3 mm, 21 mm and 19 mm respectively. The methanollic stem extract of A. paniculata showed a maximum antibacterial activity against Salmonella with zone of inhibition of 25 mm while n-hexane stem extract exhibited a maximum zone inhibition of 17.6 mm against Salmonella. The minimum inhibitory concentration (MIC) value for all the A. paniculata extracts was at a concentration of 12.5 – 50 ml. The pH of the water ranged from 6.50 to 6.90, temperature ranged from 26 to 31°C. The findings from this study demonstrated that River Owena is highly contaminated with faecal materials and that leaf and stem extracts of A. paniculata may be used as antibacterial agents against methicillin and vancomycin resistant bacteria of enteric origin.