The endothelium is fundamental for the regulation of vascular tone and structure. Under disease conditions, including the presence of cardiovascular disease risk factors, the endothelium loses its protective role and becomes a proatherosclerotic structure. In this article we searched for strategies from PUBMED and Science Direct databases using the following key words: endothelium, natural bioactive compounds, polyphenols and cardiovascular diseases. The search was restricted to english language papers. Studies have identified the contribution of diet to the risk of developing cardiovascular diseases. In this context, high intakes of fruit and vegetables are associated with the decrease of cardiovascular diseases. Thus the most important fruit/vegetables and bioactive compounds to prevent endothelial diseases are berries, apples, virgin olive oil, tomatoes, soybeans, and polyphenols, carotenoids and unsaturated fatty acids, respectively. The bioactive compounds from fruit and vegetables provide endothelial protection through the following mechanisms: improved eNOS/NO bioavailability, attenuates oxidative stress, inhibited NF-κB pathway and decreased cell adhesion molecules expression. In this article natural bioactive compound mechanisms of endothelium protection are thoroughly reviewed.