Leaves of Luffa acutangular are consumed in some parts of Nigeria as part of folk medicine for the treatment of diseases and as a vegetable food source. This study was undertaken to evaluate the phytochemical constituents from ethanol extracts, antimicrobial resistance, proximate and mineral analysis of its leaf extracts. The phytochemical investigation revealed the presence of alkaloids, phenols, saponins, tannins, terpenoids, and triterpenoids. The elemental analysis of the dried leaf revealed the presence of Calcium (58.6 mg/g), Copper (0.6 mg/g), Magnesium (12.4 mg/g), Manganese (0.9 mg/g), Zinc (0.6 mg/g), Sodium (14.4 mg/g) and Potassium (143.6 mg/g) respectively. The samples were screened against Staphylococcus aureus, Staphylococcus pneumonia, Streptococcus pyrogens, Klebsciella pneumonia, Candida albicans and Candida tropicalis for their anti-microbial activity using Ciprofloxacin, Streptomycin and Fluconazole as control. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC) values were determined. Proximate analysis revealed moisture content of 10.6%, ash 6.3%, crude protein 2.6%, crude fiber 4.0%, fat 5.1% and carbohydrate content of 71.4%. The study showed that the leaf extract of L. acutangular may be used to manage some common diseases caused by the tested organisms. The major antimicrobial activity is tailored to the phyto-constituents. This confirms the folkloric use of the plants in the management of various diseases.