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 Ventilago harmandiana (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 12 , 13 , 15 , and 16 showed activity against syncytium formation with half maximal effective concentration (EC 50 ) values ranging from 9.9 to 47 μM (selectivity index (SI) 2.4–4.5).