Endophytic fungi associated with Nigerian plants have recently generated significant interest in drug discovery programmes due to their immense potential to contribute to the discovery of new bioactive compounds. This study was carried out to investigate the secondary metabolites of endophytic fungi isolated from leaves of Newbouldia laevis, Ocimum gratissimum, and Carica papaya. The plants were collected from Agulu, Anambra State, South-East Nigeria. Endophytic fungal isolation, fungal fermentation; and extraction of secondary metabolites were carried out using standard methods. The crude extracts were screened for antimicrobial activities using the agar well diffusion method, and were also subjected to high performance liquid chromatography (HPLC) analysis to identify their constituents. A total of five endophytic fungi was isolated, two from N. laevis (NL-L1 and NL-L2), one from O. gratissimum (SL-L1), and two from C. papaya (PPL-LAC and PPL-LE2). In the antimicrobial assay, the extracts of NL-L2, SL-L1, and PPL-LE2 displayed mild antibacterial activity against both Gram negative and Gram positive test bacteria. PPL-LAC extract showed mild activity only against S. aureus, while no antimicrobial activity was recorded for NL-L1 extract. All the endophytic fungal extracts showed no activity against the test fungi C. albicans and A. fumigatus. HPLC analysis of the fungal extracts revealed the presence of ethyl 4-hydroxyphenyl acetate and ferulic acid in NL-L1; ruspolinone in NL-L2; protocatechuic acid, scytalone, and cladosporin in SL-L1; indole-3-acetic acid and indole-3-carbaldehyde in PPL-LE2; and indole-3-acetic acid in PPL-LAC. The findings of this study revealed the potentials possessed by these plants as source of endophytes that express biological active compounds. These endophytes hold key of possibilities to the discovery of novel molecules for pharmaceutical, agricultural and industrial applications.