Background: This study explores the neuroprotective role of sodium butyrate (NaB) in mitigating 6-hydroxydopamine (6-OHDA) induced damage in PC12 cells, with a focus on mental health implications via Brain-Derived Neurotrophic Factor (BDNF) and its precursor, proBDNF. Methods: We assessed cell viability using the Cell Counting Kit-8 and calculated the inhibitory concentration of 6-OHDA. Key protein expressions such as alpha-synuclein, tyrosine hydroxylase, BDNF, and proBDNF were analyzed through immunofluorescence and western blotting. We specifically examined the effects of NaB on cell viability and the BDNF/proBDNF ratio under 6-OHDA-induced stress. Results: 6-OHDA exposure led to a decrease in PC12 cell viability and alterations in key protein expressions relevant to neuronal health. Notably, NaB treatment countered these changes, particularly enhancing BDNF levels while not significantly affecting proBDNF. Conclusion: NaB demonstrates potential as a neuroprotective agent, particularly through modulating the BDNF/proBDNF ratio, underscoring its potential relevance in mental health contexts, specifically in conditions like Parkinson's disease where dopaminergic neuronal integrity is crucial. This suggests NaB's therapeutic prospects in neurodegenerative and mental health disorders.