As a major cause of neurodegeneration in the elderly, Parkinson's disease (PD) has attracted intense research attention. PD results from a decline in the numbers of dopaminergic neurons. Due to low levels of plasma exposure and the drug efflux properties of neuronal cells, orally delivering anti-PD drugs is challenging. Nanocrystals (NCs) can increase dissolution velocities and saturation solubility, improving oral bioavailability and brain uptake. In this study, Ginkgolide B (GB), a potent anti-Parkinsonism compound, was selected to verify the utility of NCs to effectively accumulate GB in both the blood and brain. Highly stabilized GB-NCs had small sizes, high rates of dissolution, enhanced cellular uptake and permeability. The GB-NCs could protect neurons against cytotoxicity induced by MPP, and showed no toxicity in zebrafish. Fluorescent imaging in zebrafish indicated high levels of the NCs in both the gut and brain. When orally administrated to rats, the GB-NCs showed higher drug plasma levels and neuronal drug distributions when compared to control groups. Importantly, in MPTP-induced PD model, GB-NCs treatment resulted in improved behavior, reduced dopamine deficiency, and elevated dopamine metabolite levels. In summary, these highlight the fabrication of GB-NCs as effective drug carriers for the neuronal delivery of anti-PD therapies.