Mercury represents one of the main environmental pollutants and human exposure to this heavy metal occurs primarily through nutritional sources, including contaminated fish. This highly toxic compound is known to pose serious threats to human health, including neurological alterations. Moreover, based on its effects on cardiovascular health, mercury exposure is now considered an independent risk factor for cardiovascular diseases. The possibility of reducing heavy metal toxicity through diet has attracted the interest of those responsible for the public health service. In this respect, the use of phytochemicals able to significantly counteract oxidative alterations as an attractive tool for the reduction of mercury toxicity has been proposed. Here we review recent evidence supporting the beneficial role of olive oil hydroxytyrosol in preventing mercury-induced alterations in both human erythrocytes and neuroblastoma cells. This novel biological effect exerted by hydroxytyrosol represents an additional mechanism responsible for the much-claimed health benefits of this dietary phenol. Taken together the reported findings encourage the use of virgin olive oil, characterized by a high hydroxytyrosol content, as an innovative approach in designing combined dietary and/or nutraceutical strategies to contrast mercury toxicity in humans.