The purpose of this work was to determine the antibacterial and antifungal activities of Datura stramonium on selected microorganisms, and to evaluate its phytochemical properties. The dry and wet leaves of D. stramonium were collected, extracted using ethanol and water, and assessed for antibacterial and antifungal activities at different concentrations (25mg, 12.5mg, 6.25mg, and 3.12mg) by disc diffusion method. The clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Salmonela typhi, Aspergillus fumigatus and Candida albicans were used. The highest zone of inhibition for bacteria was shown with ethanolic dry extract (11.3±3.4) at 25mg/ml and the lowest with aqueous dry extract (4.0±1.4) at 25mg/ml against Escherichia coli. The highest zone of inhibition for fungi was shown with ethanolic dry extract (10±1.4) at 25mg/ml against Aspergillus fumigatus and the lowest was with ethanolic wet extract (2.0±0.0) at 25mg/ml against Candida albican.The phytochemical analysis result showed the presence of tannin (1.757%), phenol (1.149%), flavonoid (6.325%), alkaloid (8.552%), phytate (2.671%), and hydrogen cyanide (4.175%). The chromatographic analysis showed the presence of over 40 elements with the highest as hydrazine (41%) and methyl hydrogen disulphide (41%). In this study, D. stramonium leaf extracts showed significant antibacterial and antifungal activities due to the presence of the phytochemical and bioactive compounds. This upholds the native utility of this plant to treat bacterial and fungal infections. Conclusively, this plant would serve as treatment alternatives for infections and basis for sources of antimicrobial agent.