Oxidative stress may play critically important roles in the etiology of Parkinson's disease (PD). 6‐Hydroxydopamine (6‐OHDA) is a physiological neurotoxin reported to induce oxidative‐induced apoptosis of dopaminergic neurons in PD mice models. Valproic acid (VPA), a clinical mood stabilizer, is a HDAC inhibitor with neuroprotective capacities. In the study, we aim at examining the feasibility of VPA as a protector for dopaminergic neurons against damage from 6‐OHDA, and the intracellular mechanisms. The 6‐OHDA‐induced neurotoxicity to the human dopaminergic cell line SH‐SY5Y was applied for examining VPA protective effects. Pretreatment with VPA was able to improve cell viability and reduce 6‐OHDA‐induced reactive oxygen species. Furthermore, a significant suppression of apoptotic caspases including cleaved caspase‐3, caspase‐7, and caspase‐9 was observed. The results also revealed VPA decreased the 6‐OHDA‐induced Bax/Bcl2 ratio, as measured at protein level. These novel findings indicate that VPA may be capable of protecting the SH‐SY5Y dopaminergic neuronal cells from 6‐OHDA‐induced toxicity via the deceasing of apoptotic caspases (cleaved caspase‐3, caspase‐7, and caspase‐9) and reducing of the Bax/Bcl2 ratio. Very possibly, VPA could serve as not only a mood stabilizer but also a potential antidote for PD prevention.