The present study investigated the role of syringic acid (SA) in the renal protection mediated through the nitric oxide synthase (NOS) pathway in rodents treated with cisplatin (CP) with a single nephrotoxic dose of 5 mg/kg (i.p.) on the day the study commenced. The nephrotoxicity caused by a single dose of CP was assessed by measuring renal functional test (in serum and urine), oxidative stress parameters, and histopathological evaluation with hematoxylin and eosin stain in renal tissue on day 5, i.e., the last day of the study. The Administration of SA provides significant (p < 0.05) dose-mediated (50 and 100 mg/kg, p.o.) nephroprotection in CP-treated male Wistar rats. Pretreatment with NOS inhibitor, L-nitroarginine methyl ester (20 mg/kg, i.p.) in rats abolished the nephroprotective prospective of SA. SA-mediated activation of the NOS pathway has been hypothesized to contribute to renoprotection.