Four new isobenzofuranone monomers, (+)-epicoccone C ((+)-1), (-)-epicoccone C ((-)-1), epicoccone D (2), epicoccone E (3) and one new isobenzofuranone dimer, epicolactone A (4), together with four known related dimers were obtained from the fermentation of an endophytic fungus, Epicoccum nigrum SCNU-F0002, which was isolated from the fresh fruit of the mangrove plant Acanthus ilicifolius L. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculations. These isolated compounds (1-8) were evaluated for their antioxidant activity and α-glucosidase enzyme inhibitory activity. All of the compounds except 5 exhibited more potent α-glucosidase inhibitory effect than acarbose. Most of the compounds showed superior antioxidant activity with IC50 values ranging from 10.2 to 15.3 μM than positive control, gallic acid and vitamin C.