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Two new diterpenoids, hypoxyterpoids A (<b>1</b>) and B (<b>2</b>), and four new isocoumarin derivatives, hypoxymarins A–D (<b>4</b>–<b>7</b>), together, with seven known metabolites (<b>3</b> and <b>8</b>–<b>13</b>) were obtained from the crude extract of the mangrove-derived fungus <i>Hypoxylon</i> sp. The structures of the new compounds were elucidated on the basis of 1- and 2-dimensional (1D/2D) nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric analysis. The absolute configurations of compounds <b>1</b>, <b>2</b>, <b>4</b>, <b>5,</b> and <b>7</b> were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra, and the absolute configurations of C-4′ in <b>6</b> and C-9 in <b>7</b> were determined by [Rh₂(OCOCF₃)₄]-induced ECD spectra. Compound <b>1</b> showed moderate <i>α</i>-glucosidase inhibitory activities with IC₅₀ values of 741.5 ± 2.83 μM. Compounds <b>6</b> and <b>11</b> exhibited DPPH scavenging activities with IC₅₀ values of 15.36 ± 0.24 and 3.69 ± 0.07 μM, respectively.