Ten new isocoumarins, named peniisocoumarins A-J (1-9 and 11), along with three known analogues (10, 12, and 13) were obtained from the fermentation of an endophytic fungus, Penicillium commune QQF-3, which was isolated from a fresh fruit of the mangrove plant Kandelia candel. Their structures were elucidated through extensive spectroscopic analysis. The absolute configurations of 1-7 were determined by single-crystal X-ray diffraction and modified Mosher's method, and those of 8, 9, and 11 were assigned on the basis of experimental and calculated electronic circular dichroism data. Compounds 1 and 2 were unusual dimeric isocoumarins with a symmetric four-membered core. These isolated compounds (1-13) were evaluated for their cytotoxicity and enzyme inhibitory activities against α-glucosidase and Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB). Among them, compounds 3, 7, 9, and 11 exhibited potent inhibitory effects against α-glucosidase with IC50 values ranging from 38.1 to 78.1 μM, and compound 7 was found to inhibit MptpB with an IC50 value of 20.7 μM.