Chromatographic separation of the crude extracts from the roots of Ventilago denticulata led to the isolation of four new anthraquinones, ventilanones L–O (1–4), together with eight known anthraquinones (5–12). Their structures were elucidated by spectroscopic methods (UV, IR, 1H NMR, 13C NMR, and 2D NMR) and mass spectrometry (MS), as well as comparison of their spectroscopic data with those reported in the literature. HDACs inhibitory activity evaluation resulted that compound 2 exhibited moderate antiproliferative activity against HeLa and A549 cell lines but nontoxic to normal cell. Molecular docking indicated the phenolic functionality of 2 plays crucial interactions with class II HDAC4 enzyme.