Seven previously undescribed compounds, including five pyranonaphthoquinones (ventilanones L-P) and two naphthoquinones (ventilanones Q and R), along with 15 known compounds were isolated from the stem bark of <i>Ventilago harmandiana</i> (Rhamnaceae). The structures were established by extensive analysis of their spectroscopic data. The absolute configuration of ventilanone L was established from single crystal X-ray crystallographic analysis using Cu Kα radiation and from its electronic circular dichroism data. Anti-HIV-1 activity using a syncytium inhibition assay and the cytotoxic activities of some isolated compounds were evaluated. Compounds <b>12</b>, <b>13</b>, <b>15</b>, and <b>16</b> showed activity against syncytium formation with half maximal effective concentration (EC<sub>50</sub>) values ranging from 9.9 to 47 μM (selectivity index (SI) 2.4-4.5).