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One new diterpenoid, diaporpenoid A (<b>1</b>), two new sesquiterpenoids, diaporpenoids B–C (<b>2</b>,<b>3</b>) and three new <i>α</i>-pyrone derivatives, diaporpyrones A–C (<b>4</b>–<b>6</b>) were isolated from an MeOH extract obtained from cultures of the mangrove endophytic fungus <i>Diaporthe</i> sp. QYM12. Their structures were elucidated by extensive analysis of spectroscopic data. The absolute configurations were determined by electronic circular dichroism (ECD) calculations and a comparison of the specific rotation. Compound <b>1</b> had an unusual 5/10/5-fused tricyclic ring system. Compounds <b>1</b> and <b>4</b> showed potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 cells with IC₅₀ values of 21.5 and 12.5 μM, respectively.