Ten secondary metabolites (1-10) including a new phenolic enamide, methyl (Z)-3-(3,4-dihydroxyphenyl)-2-formamidoacrylate (1), and a new meroterpenoid, 15-hydroxydecaturin A (2), were characterized from the EtOAc extracts of the marine alga-derived endophytic fungus Penicillium oxalicum EN-290. The structures of these compounds were elucidated on the basis of 1D and 2D NMR experiments and the absolute configuration of compound 2 was confirmed by electronic circular dichroism quantum calculations. Compound 1 showed potent activity against Staphylococcus aureus with an MIC value of 2.0g/ml, which is stronger than that of the positive control (chloromycetin, with an MIC 4.0g/ml). This compound also showed activity against harmful algal bloom causative species Nitzschia closterium with inhibition zones of 20, 16, and 10mm at 20, 10, and 5mg/ml, respectively. Interestingly, so far, this type of anti-HAB metabolites has only been found in the algal-derived isolate of P. oxalicum. It could probably be a defense of this fungus against environmental stress and threat of survival.