Mercury (Hg) is a highly toxic environmental contaminant that can harm human health, ultimately leading to endothelial dysfunction. Hg toxicity is partially mediated by the exposure of the cell membrane's surface of erythrocytes (RBCs) to phosphatidylserine (PS). In the context of these challenges, hydroxytyrosol, a phenolic compound of olive oil, has the ability to mitigate the toxic effects of Hg. This study aims to analyze the effect of Hg on the adhesion of RBCs and polymorphonuclear cells (PMNs) to the vascular endothelium and the potential protective effect of hydroxytyrosol, as these interactions are crucial in the development of cardiovascular diseases (CVDs). RBCs, PMNs, and human vein endothelial cells (HUVECs) were treated with increasing concentrations of HgCl and, in some cases, with hydroxytyrosol, and their adhesion to HUVECs and the expression of adhesion molecules were subsequently analyzed. Our results demonstrate that HgCl significantly increases the adhesion of both RBCs (2.72 ± 0.48 S.E.M., -value < 0.02) and PMNs (11.19 ± 1.96 S.E.M., -value < 0.05) to HUVECs and that their adhesiveness is significantly reduced following treatment with hydroxytyrosol (RBCs, 1.2 ± 1.18 S.E.M., -value < 0.02 and PMNs, 4.04 ± 1.35 S.E.M., -value < 0.06). Interestingly, HgCl does not alter the expression of adhesion molecules on either HUVECs or RBCs, suggesting that reduced exposure to PS is a key factor in hydroxytyrosol protection against HgCl-induced RBC adhesion to the endothelium. On the other hand, HgCl induces increased expression of several PMN adhesion molecules (CD11b 215.4 ± 30.83 S.E.M. -value < 0.01), while hydroxytyrosol inhibits their expression (e.g., CD11b 149 ± 14.35 S.E.M., -value < 0.03), which would seem to be the mechanism by which hydroxytyrosol restricts PMN-endothelium interactions. These results provide new insights into the molecular mechanisms through which hydroxytyrosol mitigates the harmful effects of Hg on cardiovascular health, highlighting its potential as a therapeutic agent that can reduce the cardiovascular risk related to heavy metal exposure.