We aimed to compare the protective effect of L-carnitine (CAR) and amifostine (AMF) against cisplatin (CDDP)-induced nephrotoxicity through biochemical markers and histopathological evaluation. Fifty-seven Wistar albino male rats were randomly classified into six groups, which were AMF+CDDP (n = 11; 200 mg/kg AMF 30 min prior to 7 mg/kg CDDP), CAR+CDDP (n = 11; 300 mg/kg CAR 30 min prior to 7 mg/kg CDDP), CDDP (n = 11; 1 mL/kg isotonic saline 30 min prior to 7 mg/kg CDDP), AMF (n = 8; 200 mg/kg AMF alone), CAR (n = 8; 300 mg/kg CAR alone), and control (n = 8; 1 mL/kg isotonic saline alone). All drugs were given intraperitoneally. Five days after medication, animals were killed, and samples of blood and kidney tissues were collected for biochemical and histopathological evaluation. The serum urea level was highest in AMF+CDDP group among CDDP-applied groups without statistical significance (median, range: 88, 56-21 mg/dL; P > 0.05). There was no statistical significance among CDDP-applied groups in terms of creatinine level (P > 0.05). In the AMF+CDDP group, the median glomerular, tubular, and tubulointerstitial inflammatory damage scores were significantly higher than the other CDDP-applied groups (P < 0.001). The difference between CAR+CDDP and CDDP groups was not statistically significant in terms of renal damage scores. AMF+CDDP group had significantly higher median total nephrotoxicity score than all the other groups (P < 0.001). To conclude, AMF or CAR has no protective effect on CDDP-induced nephrotoxicity. Furthermore, our findings suggest that application of AMF before CDDP may enhance CDDP-induced nephrotoxicity histopathologically.