Introduction: Latest findings show that the proline-rich polypeptide complex (PRP), known as Colostrinin, and its component peptides may have beneficial effects on cellular response to oxidative stress, which is the main aspect of aging and an essential feature in neurodegenerative disorders. Recently isolated and described nonapeptide NP-POL (RPKHPIKHQ) was shown to have potential protective properties in neuronal cells, including the regulation of cell survival, neurite protection and intracellular ROS release. Based on those findings, further studies were performed covering the possible effects of NP-POL on molecular and enzymatic mechanisms of response to oxidative stress. Materials/Methods: To evaluate the regulatory effects of NP-POL on oxidative stress, 6-hydroxydopamine-treated rat pheochromocytoma (PC12) cells were used as an experimental model and a series of assays were performed, including H2O2 release, glutathione turnover and the expression and activity of superoxide dismutases (Mn-SOD and Cu-Zn-SOD). Results: NP-POL was shown to modify the cellular antioxidative response to reverse the toxic effects of 6-hydroxydopamine. The direct effects of NP-POL include a significant reduction of the total amount of released H2O2 and enhanced glutathione activation. Moreover, NP-POL enhanced the expression of superoxide dismutase in untreated cells, which confirms its contribution in secondary enzymatic response. Discussion: The newly discovered peptide NP-POL, isolated from the colostrum-derived polypeptide complex Colostrinin, was shown to have potential antioxidant and neuroprotective properties, which makes it very promising as a natural therapeutic in neurodegenerative diseases.