Periconia siamensis (strain CMUGE015) was isolated from leaves of the grass, Thysanoleana latifolia (Poaceae). It was antagonistic against the human pathogens Bacillus cereus, Listeria monocytogenes, MRSA (Methicillin Resistance Staphylococcus aureus) and Pseudomonas aeruginosa the causative agents of food borne disease, Listeriosis, skin infections and lung disease, respectively. Metabolits in both culture filtrates and crude extracts of the filtrates were inhibitory against the microbes tested. The major active ingredients from the culture filtrate were purified by silica gel column chromatography and identified to be Modiolide A, 5, 8-dihydroxy-10-methyl-5, 8, 9, 10-tetrahydro-2H-oxecin-2-one (Compound 1) and 4-Chromanone, 6-hydroxy-2-methyl- (5CI) (Compound 2) by IR, NMR and mass spectral (MS) data. Bioassays showed that both compounds had antibacterial activity against all the test bacteria. Minimum inhibitory concentrations were determined to be 50 μg mL-1 for compound 1 and 100 μg mL-1 for compound 2. This is the first report of the production of these two antibacterial metabolites a terrestrial endophytic fungus.