Three new lactones penicilactones A−C (1−3) were obtained from the mangrove-derived fungus Penicillium sp. TGM112. Their structures and absolute configurations were determined by detailed NMR, MS spectroscopic data, Mo2(OAc)4-induced electronic circular dichroism (ECD), and circular dichroism (CD) spectroscopy. Compound 1 showed antibacterial activity against Staphylococcus aureus with an MIC value of 6.25 μg/mL. Compound 2 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with the LC50 value of 78.5 (±0.58) μg/mL.