This study reports the protective role of Clerodendron glandulosum (CG) extract against in vitro LDL oxidation and Ox-LDL induced macrophage apoptosis using various experimental models. Effect of CG extract on Cu(2+) mediated LDL oxidation kinetics and formation of various intermediary products and its ability to prevent human monocyte derived macrophage mediated LDL oxidation have been investigated. Ox-LDL induced macrophage apoptosis was evaluated by nuclear condensation, cell cycle analysis, and annexin V-FITC/PI staining in presence or absence of CG extract. Results recorded in the present study clearly suggest the protective role of CG extract against LDL oxidation and Ox-LDL induced macrophage oxidative stress, mitochondrial dysfunction, and apoptosis. This is the first report on the protective role of CG extract on two key events of atherosclerosis portending its possible therapeutic use as an anti-atherogenic herbal medicine.