Simpterpenoid A (1), an unprecedented meroterpenoid possessing a highly functionalized cyclohexadiene moiety (ring C) featuring gem-propane-1,2-dione and methylformate groups, was characterized from mangrove-derived Penicillium simplicissimum MA-332. Due to the highly oxygenated and functionalized ring C and lack of some key correlations, the unambiguous assignment of the planar structure and steric configuration was solved by X-ray crystallographic analysis. Compound 1 exhibited inhibitory activity against influenza neuraminidase in nanomolar quantities.