The aim of this experimental study was to investigate the protective effect of Ganoderma lucidum capsules against colistin nephrotoxicity. The study animals were separated into four groups: control, colistin (9 mg/kg), colistin-G. lucidum 50 mg/kg, and colistin-G. lucidum 100 mg/kg. In the colistin group, serum blood urea nitrogen and creatinine values were found to be higher than those of the other groups (p < 0.001). The malondialdehyde, catalase, total oxidative stress, oxidative stress index, and oxidized glutathione values in serum and kidney tissue samples were determined to be higher in the colistin group than in the other groups (p < 0.001). The total antioxidative stress, superoxide dismutase, glutathione peroxidase, and glutathione values measured in the serum and kidney tissue samples were determined to be lower in the colistin group (p < 0.001). Oxidative stress is responsible for tubule damage in colistin nephrotoxicity, and when G. lucidum is used together with colistin, renal damage is reduced.