Aqueous and ethanolic leaf extracts of Dennetia tripetala and Psidium guajava were evaluated for their antimicrobial effects against clinical isolates of Staphylococcus aureus and Escherichia coli from Annunciation Specialist Hospital Enugu State Nigeria. The identified isolates were sub-cultured on sterile nutrient agar plates and incubated over night at 37°C. The identified isolates were then re-identified and characterized. Polymerase chain reaction (PCR) was used to detect Staphylococcus aureus strain which has 85% pairwise similarity with Staphylococcus haemolyticus strain SH1 and Escherichia coli strain which has 99.62% pairwise similarity with E. coli strain AC1. Quantitative and qualitative phytochemical analysis were done on the extracts of Dennetia tripetala and Psidium guajava using water and ethanol as extracting solvents. The phytochemical screening of the extracts revealed the presence of tannins, saponins, alkaloids, flavonoids, glycosides and phenols. Quinonas however, was absent in this study. The isolates were screened for sensitivity to different extracts using agar well diffusion technique. The results indicated that both the ethanol and aqueous extracts of the Psidium guajava leaves showed inhibitory activity against Staphylococcus aureus at 10mm and 12mm respectively but no activity against E. coli. On the other hand, the aqueous extracts of the Dennetia tripetala showed inhibitory activity against S. aureus and E. coli at 20mm and 10mm respectively whereas, the ethanol extract has no activity on both test microorganism. The extracts were reconstituted with Dimethyl sulfoxide (DMSO) to concentrations (mg/ml) of 200, 100, 50, 25, 12.5 and the minimal inhibitory concentration (MIC) of the extracts were determined using agar well method. The MIC of the Psidium guajava leaves extract revealed that both ethanolic and aqueous extracts inhibited S. aureus at 12.5mg/ml. While MIC of the Dennetia tripetala revealed that the aquous extract inhibited S. aureus at 50mg/ml and E. coli at 100mg/ml from the results, the aqueous extracts of both plants generally have a better inhibitory property than the ethanolic extracts. Based on the present findings, Dennetia tripetala and Psidium guajava leaves possess the capability of being good candidates in the search for a natural antimicrobial agent against infections or diseases caused by Staphylococcus aureus and Escherichia coli.