Chermesins A-D (1-4), four new spiromeroterpenoids containing a drimane-type sesquiterpene skeleton, were isolated and identified from the culture extract of Penicillium chermesinum EN-480, an endophytic fungus obtained from the inner tissue of the marine red alga Pterocladiella tenuis. The structures of these new spiromeroterpenoids were elucidated based on detailed spectroscopic analyses, and their absolute configurations were confirmed by single-crystal X-ray diffraction experiments and by ECD data. This is the first report of the crystal structures of spiromeroterpenoids that contain a drimane-type sesquiterpene skeleton with a rare cyclohexa-2,5-dienone unit, which resulted in the unambiguous assignment of their relative and absolute configurations. Compounds 1 and 2 exhibited antibacterial activity against the opportunistic pathogen Micrococcus luteus, with an MIC value of 8 μg/mL.