Abstract: In vitro antibacterial activities of four fractions of stem bark of Distemonanthus benthamianus Baill. against some bacterial isolates implicated in oro-dental infections were investigated using standard microbiological methods. The aqueous and chloroform fractions exhibited significant inhibitory action against all twelve bacterial isolates tested at a concentration of 10 mg mL-1. The zones of inhibition due to the aqueous fraction ranged between 10 and 15 mm while that of chloroform fraction ranged between 8 and 13 mm. The Minimum Inhibitory Concentration (MIC) exhibited by aqueous fraction against the bacterial isolates ranged between 0.625 and 2.5 mg mL-1 while that of chloroform fraction ranged between 0.313 and 5.0 mg mL-1. Phytochemical analysis of Distemonanthus benthamianus extract revealed the presence of tannins, steroids, saponins and alkaloids. Between 18 and 76% of Streptococcus mutans were killed within 120 min contact time in aqueous extract concentration of between 0.3125 and 2.50 mg mL-1, while between 15 and 60% of Bacteroides gingivalis were killed within the same period and concentration by the aqueous fraction of the crude extract. The same concentrations of extracts resulted in protein leakages in the test organisms and we proposed disruption of cell membrane as a mechanism of action of the plant extract.