Fish by-products may become more than 50% of the starting material. If mismanaged, these large quantities of by-products can create serious pollution problems cost associated to disposal. Enzymatic hydrolysis is one of the techniques that are currently being developed in order to and add value to these biomolecules. Enzymatic protein hydrolysates allow the release of peptides with several bioactivities such as antioxidant, antimicrobial, antihypertensive among others. Moreover, another bioactivity of protein hydrolysates which is gaining attention is the neuroprotective ability. The brain is and organ extremely susceptible to oxidative stress damage. Oxidative stress is involved in the occurrence of neurodegenerative diseases such as Parkinson and Alzheimer's. Cell system Ht-22 is a cell line obtained from mouse hippocampus which is a vertebrate brain structure responsible form the consolidation of short-term to long-term memories. The objective of the present study was to evaluate the neurodegenerative effect in Ht-22 cell system of common carp by-products (CCB) protein hydrolysate. CCB were hydrolyzed using the enzyme Protamex to degree of hydrolysis of 15%. Cell viability was determined by the MTT assay which measures de mitochondrial dehydrogenases activity. Intracellular reactive oxygen species (ROS) was measured by fluorescence. Results indicated that the hydrolysate presented no cytotoxicity. Moreover, results showed that even at the lowest concentration (0.06 mg/ml) the growth of Ht-22 cells was promoted. Additionally, hydrolysates exposure to Ht-22 cells showed a decrease in intracellular ROS production at the highest hydrolysate concentration (1.25 mg/ml). This decrease in intracellular ROS could be due to the amino acid constituents and the sequence of the peptides of the hydrolysate. This work demonstrated that it is feasible to produce hydrolysates showing neuroprotective activity in Ht-22 cells by decreasing ROS production from common carp by-product. Further in vivo studies in animal models are necessary to evaluate the possible health benefits of hydrolysates.