Fresh samples of leaves of Acacia nilotica were investigated for phytochemical and antimicrobial activities. The sample was air-dried under shade and grounded to powder. For solvents (n-hexane, ethyl acetate, methanol and water) were used to extract the samples. The samples were screened for alkaloids, tannins, saponins, resins, phenolics, glycosisdes, anthraquinones and proteins. Antimicrobial screening was carried out using disk diffusion method. The tested organisms are Escherichia sp, Candida albicans, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, Proteuns species, Klebesiella pneumoniae, Aspergillus fumigatus and Epidermphyton floccosium. The minimum inhibitory concentration (MIC) of four of the above organisms were carried out. Result of the antimicrobial analysis indicated that the methanol extract of the leaves (Mel) showed antimicrobial activity against E. coli (14.5mm) Staphylococcus aureus (12.0mm), Pseudomonas aeruginosa (14.5mm) Proteus spp (11.5mm), Klebsiulla Pneumoniae (10.0mm),Bacillus subtilis (9.0mm), Candida albicans (8.5mm), Aspergillus fumigatus (8.0mm) and Epidermyphyton floccosium (5.0mm). The least MIC was recorded for Pseudomonas aeruginosa (0.41 g/cm3). The results obtained in these studies showed that Acacia nilotica possess some antimicrobial activity while the phytochemical analysis revealed the presence of saponins, tannins, phenils and resins, which has hitherto been reported to have medicinal properties.