The present study was conducted to compare between the protective effect of either garlic or vitamin E (Vit E) against hepatic and renal damage induced by 100mg/ kg linezolid (LNZ) administration. Thirty male albino rats were allocated into equal six groups; first three control groups; (control, tween 80 and olive oil); Group4; received 100mg LNZ / kg for 14 consecutive days. The last two groups were administered either garlic (500 mg/kg) or Vit E (100 mg/kg) prior to LNZ administration daily for 14 consecutive days. Blood samples were obtained from all rats for biochemical investigations and oxidative stress biomarkers. Specimens from liver and kidneys were excised for histopathological investigation. Linezolid induced a significant elevation in serum Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and urea. Alterations in antioxidant / oxidant status were noticed during LNZ administration. Administration of garlic or Vit E modulated the previous parameters and restored histological structures. In conclusion, both garlic and Vit E were able to ameliorate hepato-renal alterations induced by LNZ via their antioxidant effects.