Abstract. The viability of microorganisms can be determined by the total dehydrogenase activity (DHA). Thus, a reduction in total dehydrogenase activity is an indication of the bactericidal effect of plant extract. The antimicrobial potentials of ethanol extract of Combretum dolichopentalum (EECD) leaves on microbial isolates from stool, degenerated wound, and high vaginal swab were determined by the total dehydrogenase activity. The microbial cells were standardized in a spectrophotometer to an optical density of 0.70 at 420 nm and used as standardized cell suspension (inoculum) in the dehydrogenase assay. The results obtained indicated that EECD leaves were effective antimicrobial agents against Escherichia coli, Staphylococcus aureus, Salmonella typhi and Streptococcus pneumonia isolates. Threshold inhibitory concentrations of the extracts showed that EECD leaves inhibited dehydrogenase activity in all the organisms in a dose dependent manner. At 355.78 μg/ml, EECD leaves achieved an IC 50 against E. coli, and at 349.42 µg/ml and 843.80 µg/ml EECD obtained an IC 50 against Streptococcus pneumonia and Staphylococcus aureus respectively. Also, at 2270.68 μg/ml EECD leaves eliminated 100 % S. typhi to achieve 100 % inhibiting concentration. C. dolichopentalum makes a promising drug with bactericidal effect especially against Escherichia coli and Salmonella typhi.