This research evaluated the comparative antimicrobial analyses of the leaf and stem extracts of Telfairia occidentalis. The Bacterial isolates used in this work were two Gram-positive and two Gram-negative. Staphylococcus aureus and Bacillus subtilis for Gram-Positive Bacteria, Escherichia coli and Samonella typhi for Gram-negative bacteria. Nutrient Agar was the media used, and it was prepared according to the manufacturer directives. Microbial resistance to several antibiotics is becoming a source of challenge and concern to public health. In view of the increasing rate of antimicrobial drug resistance ravaging not only the African continent, but the world at large, alternative, effective and affordable substitutes is essential if bacterial infections are to be properly controlled. The result of this study supports the use of the leaf and stem parts of Telfairia occidentalis for medicinal purposes. The extent of sensitivity of the test organisms to the extracts of plant parts was assessed. Results showed the antimicrobial activity of Telfairia occidentalis leaf and stem extracts using different extracting solvents. The results revealed that the ethanol extract of the leaf of Telfairia occidentalis was most effective against the test organisms than the aqueous extracting solvent. Using ethanol as the extracting solvent, Bacillus subtilis showed the highest susceptibility (9.17 ± 2.02) to the leaf extract, while Salmonella typhi showed the least susceptibility (4.67 ± 1.04). Using aqueous extract, Escherichia coli showed the highest susceptibility (5.83 ± 3.40) to the leaf extract, while Bacillus subtilis showed the least susceptibility (3.33 ± 2.08). The results also revealed that the ethanol extract of the stem of Telfairia occidentalis was most effective against the test organisms than the aqueous extracting solvent. Using ethanol as the extracting solvent, Escherichia coli showed the highest susceptibility (6.83 ± 6.11) to the stem extract, while Bacillus subtilis showed the least susceptibility (5.16 ± 5.03). However, using aqueous extract, Bacillus subtilis showed the highest susceptibility (2.17 ± 1.60) to the leaf extract, while Escherichia coli showed the least susceptibility (1.5 ± 1.5). This is in agreement with the observations of , who concluded that the stronger extraction capacity of ethanol could have been responsible for the higher antimicrobial activity. Telfairia occidentalis leaf and stem are very rich source of bioactive compounds and the intake of these plants chemicals have a protective potential against some tropical disease in the use of leaf in folk medicine in Nigeria.