Recent evidence has shown that salmon calcitonin (sCT) has positive effects on the nervous system.However, its effect and mechanisms on glutamate-induced cytotoxicity are still unclear. The current experiment was designed to examine the effect of sCT on glutamate-induced cytotoxicity in C6 cells, involving the in ammatory and nitric oxide stress pathways. The study used the C6 glioma cell line. Four cell groups were prepared to evaluate the effect of sCT on glutamate-induced cytotoxicity. The control group was without any treatment. Cells in the glutamate group were treated with 10 mM glutamate for 24 h. Cells in the sCT group were treated with various concentrations (3, 6, 12, 25, and 50 µg/mL) of sCT for 24 hours. Cells in the sCT + glutamate group were pre-treated with various concentrations of sCT for 1 hour and then exposed to glutamate for 24 hours. The cell viability was evaluated with an XTT assay. Nuclear factor kappa b (NF-kB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), caspase-3, and caspase-9 levels in the cells were measured by ELISA kits. Apoptosis was detected by ow cytometry method. sCT at all concentrations signi cantly improved the cell viability in C6 cells after glutamateinduced cytotoxicity (p < 0.001). Moreover, sCT signi cantly reduced the levels of NF-kB (p < 0.001), TNFα, and IL-6 levels (p < 0.001). sCT also decreased nNOS, NO, and cGMP levels (P < 0.001). Furthermore, it decreased the apoptosis rate and increased the live-cell rate in the ow cytometry (P < 0.001). In conclusion, sCT has protective effects on glutamate-induced cytotoxicity in C6 glial cells by inhibiting in ammatory and nitric oxide pathways. sCT could be a useful supportive agent for people with neurodegenerative symptoms.