Cisplatin is one of the most potent and commonly used anticancer compounds to treat various tumors, but it causes many unwanted side effects that restrict its use. Hepatotoxicity is one of the common adverse effects that occur even when small amounts of cisplatin are used for short times. This study tested the ameliorative effect of fampridine, a compound used to treat multiple sclerosis, against cisplatin-induced hepatotoxicity. Forty rats were divided into four groups; Group 1 served as the negative control and did not receive any treatment; Group 2 was a positive control and administered a single intraperitoneal dose of cisplatin (5 mg/kg); Group 3 was given oral fampridine at 4 mg/kg for three consecutive days, starting from the day cisplatin was injected; Group 4 was given fampridine (4 mg/kg for three days) and cisplatin (5 mg/kg, single dose). After the experiments, animal weights, liver weights, serum creatinine, and levels of malondialdehyde (MDA) and oxidized (GSSG) and reduced glutathione (GSH) in the liver tissues were measured after three and five days of treatment. Cisplatin caused hepatotoxicity manifested by decreased body weight, liver weight, and liver-to-body weight ratios. It also elevated creatinine concentrations in the serum and MDA and GSSG in the liver tissue, while GSH concentration decreased. Fampridine treatment ameliorated these toxic impacts from cisplatin. Hence, people taking cisplatin as an anticancer therapy and fampridine as a treatment for multiple sclerosis may benefit from the latter's protective effect against cisplatin-induced hepatotoxicity.