Amikacin (AK) has long been used as an effective antibiotic to prevent Gram-negative infections. Despite its numerous benefits, Amikacin has considerable hepato-renal toxic adverse effects. The potential preventive benefits of NSO, “Nigella sativa oil" and/or ALA, “Alpha lipoic acid" were investigated in rabbits with Amikacin-induced acute hepato- renal injury. Rabbits were treated with AK (100mg/kg BW/day I/M injection) alone or with NSO (2ml/kg BW orally) and /or ALA (50 mg/kg BW/day) daily for seven days. Serum biochemical parameters well as tissue oxidative stress indicators were measured to evaluate hepato-renal damage. Rabbits administered AK showed substantial changes in serum biochemical hepato-renal damage indicators with reduction in tissue antioxidant biomarkers and rise in hepato-renal oxidant. NSO plus ALA treatment potentially alleviated the AK induced changes in blood and tissue biochemistry. The current study found that NSO and/or ALA could ameliorate the harmful effects of AK via free radicals scavenging plus their antioxidants effects.