Abstract The ethanol, methanol, n-hexane and aqueous extracts of Gnetum africanum leaves were investigated for phytochemical studies and antibacterial assay using Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Penicillium chrysogenum and Aspergillus fumigatus. The phytochemical analysis revealed the presence of tannins, saponins, glycosides, steroids in varying amount and the absence of flavonoids and anthraquinones. The antimicrobial assay for the bacterial strains showed that, n-hexane extracts exhibited the highest zone of activity against Escherichia coli, aqueous extract showed the highest activity against Staphylococcus aureus while the ethanol extract showed the highest activity against Pseudomonas aeruginosa at a minimum inhibitory concentration (MIC) of 62.5mg/ml respectively. Aqueous extract exhibited the highest against P. aeruginosa and the lowest zone against P. aeruginosa. There was relatively high antifungal activity, particularly against Penicillium chrysogenum for all the solvent extracts except for the n-hexane extracts. Generally, the methanol extract exhibited more activity than the others. The study justifies that Gnetum africanum leaves possess pharmacological properties and therefore can be use as medicinal plants for treatment of microbial infections and diseases.