Cisplatin is one of the widely used chemothrapeutic agents. One of the major side effects of the drug is renal toxicity. The aims of the presented study was (1) to investigate the effect of cisplatin on some renal metabolic enzyme activities such as hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) in an experimental model of acute renal failure and (2) to examine the protective role of erdosteine, an expectorant agent which has also antioxidant properties on cisplatin-induced nephrotoxicity and the enzyme activities mentioned above. Female Wistar albino rats were divided into three groups: sham operation group (n = 6). cisplatin group (n = 9), erdostein + cisplatin group (n = 8). All the chemicals used were applied intraperitoneally. Hexokinase, G6PD, LDH, and MDH activities were determined in the kidney supernatant at the end of the surgical procedures. Spectrophotometric methods were used to determine the activities of above-mentioned enzymes in the kidney tissue.