Parkinson’s disease (PD) is a disorder with a high prevalence, having an incidence rate in populations of 4.5 to 19 per 100000 per year. Effective prevention, reduction of morbidity and mortality, and improvements in the quality of life for survivors remain the major targets for developing new therapies for PD. However, poor oral bioavailability and limited drug penetration across the blood-brain barrier (BBB) prevent many drugs taking their therapeutic effects. Therefore, to fulfill this unmet clinical need, a substantial number of researchers have been looking for active components from herbal medicines in recent years. Our previous studies have demonstrated that Schisantherin A (SA) and baicalein provide significant protection against 6-hydroxydopamine (6-OHDA)- or 1-methyl-4- phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in zebrafish and mouse models of PD. However, the great anti-Parkinsonian potential is challenged by their poor water solubility, low bioavailability, rapid serum clearance, and MRP2-mediated efflux. To address these problems, we first formulated SA into nanocrystals (SA-NCs). The obtained SA-NCs showed not only improvement in in vitro dissolution but also enhanced oral bioavailability and increase in its brain uptake. The superior pharmacokinetic performance of SA-NCs thus paves the way to further develop SANCs as a potential therapeutic treatment for PD. Furthermore, the improved delivery of SA-NCs through the oral route to the brain suggested that nanocrystals could be a potential solution to other Biopharmaceutics Classification System (BCS) Class II natural products that encountered similar delivery challenges. Next, we studied SA nanoparticle formulation by encapsulating SA into methoxy iv poly (ethylene glycol)-block-poly (D, L)-lactic-co-glycolic acid (mPEG-PLGA) nanoparticles (SA-NPs). Small-sized SA-NPs extended SA circulation in the bloodstream and consequently resulted in an increased brain uptake. These findings demonstrated that SA-NPs could be alternative oral formulation to SA-NCs and could provide potential therapeutics for the treatment of PD. Finally, we developed Pluronic P85/F68 micelles carrying baicalein (B-MCs) with an aim to overcome multidrug resistance-associated protein 2 (MRP2)-mediated efflux and to improve its anti-Parkinsonian efficacy. The findings provide a foundation for understanding the mechanism of reversing MRP2 by Pluronic micelles better and designing more effective nano drug carriers for the treatment of PD. In summary, our findings indicated that Chinese herbal medicine, with the aid of nanotechnology, may play a noteworthy role in discovering new drug candidates and strategies for the treatment of PD.