Schizostachyum diﬀusum is used as a medicinal plant to treat ailments that deal with microbial infections. The study aimed to determine the antimicrobial activity of S. diﬀusum against Staphyloccocusaureus, Escherichia coli, Aspergillus niger, and Candida albicans. Phytochemical analysis revealed the presence of tannins, steroids, ﬂavonoids, terpenoids, phlobotannins, and coumarins. Anti microbial activity of the aqueous and methanolic leaf extracts were evaluated using the Kirby-Bauer Diﬀusion test. The highest anti-microbial potential observed was the methanolic extract which inhibited the growth of C. albicans. The result show that the diﬀerent experimental units and treatment consisting of the control has significant diﬀerence at 1% level. The other sources of variation, namely the type of extract and the replications, did not exhibit interaction eﬀects.