Neuronal cell model line SHSY-5Y is extensively adopted when in vitro investigations are related to Parkinson disease (PD) application. Herein, chitosan nanoparticles (CS NPs) were formulated for the co-administration of dopamine (DA) and Grape Seed Extract (GSE) with the aim to gain insight into the interactions occurring between SHSY-5Y and NPs. Following the ionic gelation technique, the mean particle size of the NPs resulted in the range 310–330 nm and the zeta measurements were in the range +16.4 – +35.5 mV. The presence of CS chains on the surface suggested by positive zeta values was also confirmed by FT-IR analysis, whereas storage stability studies upon different temperatures evidenced that, although aggregation occurred, DA autoxidation was prevented because no black suspensions were detected over the time, irrespectively of the temperature assayed. From a biological viewpoint, release studies of CS NPs loaded with DA and GSE showed that in SHSY-5Y cell lines DA accumulation was time-dependent, irrespectively of the presence of GSE. Furthermore, ROS levels and carbonylated proteins both decreased in SHSY-5Y cell line once NPs administering both DA and GSE were incubated, suggesting a significative reduction of oxidative stress which plays a significative role for PD development.