Amikacin (aminoglycoside) antibiotics frequently used in the treatment of Gram-negative bacterial infection in neonates, but its usage restricted due to nephrotoxicity and ototoxicity as a major side effect. The current study was concluded to examine the possible potential effect of piceatannol on nephrotoxicity induced by Amikacin in neonatal rats. Swiss Albino (Wistar) new born rats were used for the current study. The new born rats were divided into the following groups: Group I: rats treated with saline; Group II: treated with Amikacin (1200 mg/kg); Group III: treated with Amikacin+piceatennol (10 mg/kg); Group IV: treated with Amikacin+piceatennol (20 mg/kg), respectively. The antioxidant and renal parameter were scrutinized. Amikacin control group rats showed the enhanced level of Nitric Oxide (NO) and Malonaldehyde (MDA), which was significant (P<0.001) restore to the level near to the normal control treatment with piceatannol. Amikacin group demonstrated the low level of Glutathione Peroxidase (GPx) and the treatment with piceatannol significantly increase the level of GPx at dose dependent manner. The Catalase (CAT) and Superoxide Dismutase (SOD) level were not significant in the all group of rats. The level of the insulin like growth factor-1 was higher in the Amikacin control group rats, which was significantly reduced by the piceatannol at the dose-dependent manner, but the level of insulin like growth factor-1 was not reached near the normal control. During the histopathological observation, amikacin control rats showed the renal toxicity via injury in the tubular epithelial and expansion of renal necrosis. The piceatannol group rats confirmed the protective effect on the renal toxicity via improvement the renal damage induced by amikacin. Amikacin-induced nephrotoxicity is associated with oxidative stress and is confirmed by histopathological and biochemical findings. Piceatannol can be beneficial renal protective agents for modulating the amikacin-induced nephrotoxicity in neonates.