Endophytic microorganisms are recognized as potential source of novel chemical molecules that might be useful in the treatment of infectious diseases. In this study, six medicinal plants (Morinda citrifolia, Plumeria rubra, Artocarpus altilis, Musa nana, Sansevieria trifasciata and Saccharum officinarum) traditionally. They are used for treatment or management of symptoms such as cough, fever and skin diseases, were investigated for the antimicrobial activity of metabolites produced by endophytic microorganisms. Seven endophytes were isolated using the mycological media, potato dextrose agar (PDA). Three of the endophytes were identified as fungi from the Aspergillus species, three as actinomycetes and one as a gram negative bacterium. All endophytic isolates were subjected to anti-bacterial, anti-tuberculosis (TB), anti-fungal, anti-HIV, and cytotoxicity assays using micro-broth dilution assay technique in sterile 96-well plates. All isolates displayed antimicrobial activity inhibiting at least one of the test pathogens at the concentration of 100μg/ml. Of the 7 endophytic isolates, 6 isolates were active against TB, 7 were active against the bacterial test pathogens, and 2 were active against fungi while none were active against HIV. From the 7 isolates, 3 were non-toxic to mammalian cells at a concentration of 100μg/ml.