Endophytic fungi have demonstrated a harmless relationship living within the internal tissues of several plant hosts and at the same time produce diverse important bioactive compounds having a wide range of pharmaceutical applicability. In this study, nine endophytic fungi, eight from Cassava leaf: Clg1, Clg2, Clr4, Clr5, Clr6, Clr7, Clr9 and one from Cassava mid-rib: CRs3 with distinct cultural features were isolated from healthy leaves of Manihot utilisima and axenic cultures were fermented on sterile rice medium for 21 days. The antimicrobial and antioxidant activities of the fungal crude extracts were evaluated. Chemical analyses of the metabolic profiles of each fungal extract revealed the presence of nine known compounds with established biological activities. Each fungal extract exhibited antimicrobial activities against at least one Gram positive and Gram negative bacteria with an inhibition zone that ranged from 2 – 6 mm. Clg2 and CRs3 fungal extracts demonstrated moderate potential to scavenge free radical with an inhibition of 58 and 60% respectively. Septicine, cyclo(prolylvalyl), pentenedioc acid, neurolenin B, rubrofusarin, p-Hydroxybenzoic acid, protocatechuic acid, citreoisocoumarin, palitantin and pestalio pyrone were the compounds detected in the fungal fermentation products. Our findings reveal that M. utilisima leaves harbor endophytic fungi with unique chemodiversity of bioactive secondary metabolites needed for development of new drugs.