A new meroisoprenoid (<b>1</b>), two heptenolides (<b>2</b> and <b>3</b>), two <i>C</i>-benzylated flavonoids (<b>4</b> and <b>5</b>), and 11 known compounds (<b>6</b>-<b>16</b>) were isolated from leaf, stem bark, and root bark extracts of <i>Sphaerocoryne gracilis</i> ssp. <i>gracilis</i> by chromatographic separation. The structures of the new metabolites <b>1</b>-<b>5</b> were established by NMR, IR, and UV spectroscopic and mass spectrometric data analysis. (<i>Z</i>)-Sphaerodiol (<b>7</b>), (<i>Z</i>)-acetylmelodorinol (<b>8</b>), 7-hydroxy-6-hydromelodienone (<b>10</b>), and dichamanetin (<b>15</b>) inhibited the proliferation of <i>Plasmodium falciparum</i> (3D7, Dd2) with IC<sub>50</sub> values of 1.4-10.5 μM, although these compounds also showed cytotoxicity against human embryonic kidney HEK-293 cells. None of the compounds exhibited significant disruption in protein translation when assayed in vitro.