In order to understand the protective impact of kaempferol, MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was applied in hydrogen peroxide-treated human umbilical vein endothelial cells (HUVECs). The hydrogen peroxide-induced apoptosis was gauged using flow cytometry whereas western blotting was applied to detect the expression of key cellular markers in oxidation pathways. The data indicate that a total of 50 µmol/l concentration of kaempferol can profoundly protect the oxidative damage in HUVECs. However, compared to the oxidation-treated cells, the apoptosis rate was significantly decreased in drug-treated cells. Mechanistically, the percentage of G1 phase and S phase cells in vitamin C and drug groups was decreased, and the percentage of G2 phase cells was increased significantly. Intriguingly, the number of CD105/CD62E-marked HUVECs cells was markedly observed. In comparison to the oxide-treated cells, the expression level of p16, p53, p21 and Bax protein was reduced significantly in the drug-treated cells and the expression level of Bcl-2 protein increased significantly. Taken together, kaempferol can inhibit cell apoptosis by protecting the oxidative damage in HUVECs, possibility by reducing p16, p53, p21 and Bax protein expression and increasing the Bcl-2 protein expression levels in the HUVECs cells. These finding underlay some of the key markers associated with the hydrogen peroxide induced oxidative damage and may guide future therapeutics, and pharmaceutical interventions.