Objective: Injury of the spinal cord is studied in two separate mechanisms as primary and secondary injuries. During the secondary injury,spinal cord damage and related neurological defects could increase mostly because of oxidative damage. Treatments targeting this process arepromising for reducing neuronal damage. Ganoderma lucidum (GL) has the potential to suppress the inflammatory response and oxidative stress.The aim of this study is to determine the neuroprotective effect of traditional GL hot-water extract during the secondary spinal cord injury (SCI)period on an experimental rat spinal trauma model by measuring the biochemical parameters.Materials and Methods: A total of 34 rats were distributed randomly into 4 groups as trauma, vehicle, low-dose medication group (low-DMG)and high-dose medication group (high-DMG). A modified Walsh-Tator clip was applied extradurally to form an experimental SCI model. GL liquidextract was performed in medication groups with low and high (10 times higher) oral doses. Spinal cord specimens were collected after 5 daysof treatment for biochemical analysis.Results: In the low-DMG, both diphenypicrylhydrasyl (DPPH) and malondialdehyde (MDA) values were found statistically negligible whencompared with the trauma group. Comparison of the Low-DMG and vehicle group showed a significant change in DPPH value, but an insignificantchange in MDA value. A statistically significant positive change in both DPPH and MDA values was found in High-DMG when compared to traumaand vehicle groups.Conclusion: Prevention of secondary SCI is very important, since the neurological condition of the patients may get worse during this period.Dose-dependent positive results were obtained in the favor of GL in terms of both antioxidant efficacy and prevention of lipid peroxidation afterSCI. The results of this biochemical study is supporting the previous studies and showing that GL has the potential of reducing posttraumaticoxidative damage in the spinal cord when given at the appropriate dose.