Lipid peroxidation (LP) and brain edema are important factors that produce tissue damage in head injury. The purpose of this study was to investigate the effect of mexiletine, gingko biloba extract (EGb 761), and their combination on LP and edema after moderate head trauma. Forty rats were randomly and blindly divided into four groups of ten animals each: control group (bolus injection of physiological saline), mexiletine group (50 mg/kg per injection), EGb 761 group (30 mg/kg per injection), and mexiletine plus EGb 761 group (50 mg/kg and 30 mg/kg per injection, respectively). The injections were given intraperitoneally at 1 h, 9 h, and 17 h after trauma. Twenty-four hours after injury, the rats were killed, and malondialdehyde (MDA) levels and brain water content were determined. Rats treated with mexiletine, EGb 761, and mexiletine plus EGb 761 had significantly lower MDA levels than the control group (P<0.01). The lowest MDA levels were measured in the mexiletine plus EGb 761 group. However, there was no significant difference in brain water content between treated groups and the control group (P>0.05). These findings show the usefulness of mexiletine and its combination with EGb 761 as a cerebroprotective agent in this model of experimental head injury.