Parkinson’s Disease (PD) is the second most prevalent neurological disorder. Natural therapies are becoming more popular for preventing disease onset. Clove Essential Oil (CEO), a potent antioxidant derived from Syzygium aromaticum buds, was tested in vitro (SH-SY5Y) and in vivo (PD rat model) for its ability to protect against 6-OHDA-induced cell death. Twenty-four hours of SH-SY5Y cells’ exposure to 6-OHDA (100μM) drastically decreased cell viability. At doses lesser than 20μg/ml, CEO and its main component Eugenol (EG) had no cytotoxic effect on SH-SY5Y. CEO and EG at doses of 2.5-20μg/ml provided significant neuroprotection against 6-OHDA-induced cell death. A PD rat model was generated by injecting 6-OHDA (21μg/animal) unilaterally into the striatum. An assessment of motor performance can predict neuronal cell loss in the Substancia Nigra Compacta (SNc). Compared to 6-OHDA-lesioned, CEO-treated (10mg/Kg) rats’ locomotor performance (actimetry and cylinder tests) improved significantly one and two weeks after 6-OHDA-lesion. Tyrosine Hydroxylase (TH) cell count showed a significant decrease in cell death in ipsilateral SNc in both CEO-treated and 6-OHDA-lesioned rats when compared to contralateral. In contrast to the 6-OHDA-lesioned group, the ipsilateral SNc of the CEO-treated group showed a significant high TH cell number. In the present study, the neuroprotective effect of CEO was demonstrated both in vitro and in vivo against 6-OHDA cytotoxicity. Therefore, CEO could be used as a food supplement for PD prevention.