Resveratrol, a natural phytochemical found in grapes and red wine, has been found to possess protective effects against endothelial cell apoptosis and oxidative damage. Oxidized-low density lipoprotein (ox-LDL) can induce apoptosis of endothelial cells, which is an important initial event in several cardiovascular diseases. However, the effect of resveratrol on ox-LDL-induced apoptosis and oxidative damage, and the possible associated mechanisms remain to be elucidated. In the present study, following exposure to ox-LDL, human umbilical vein endothelial cells (HUVECs) were treated with or without resveratrol. Cell viability was examined using Cell Counting Kit-8 and 5-bromo-2′-deoxyuridine uptake assays, respectively. Cell apoptosis was determined by flow cytometry. Apoptosis-associated markers were detected using western blot analysis. Oxidative stress was analyzed using molecular and biochemical approaches. Resveratrol restored ox-LDL-induced HUVEC injury and apoptosis in a dose-dependent manner. In addition, compared with the control group, ox-LDL treatment decreased the B cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein ratio, mitochondrial membrane potential and activation of superoxide dismutase, and enhanced the release of mitochondrial cytochrome c into the cytoplasm, the activation of caspase and lipid peroxidation. All these alterations were significantly inhibited following treatment with resveratrol. The results demonstrated that resveratrol prevented HUVEC apoptosis through inhibiting mitochondria-derived oxidative damage. These findings may provide a novel mechanism by which resveratrol prevents against endothelial cell apoptosis.