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Introduction: Natural extracts are a suitable alternative in reducing the harmful effects of drugs and chemicals. Aim of the Work: evaluated the role of the spirulina in reducing pathological tissue lesions in the liver and kidneys of gentamicin-treated rats, as well as the relationship between these effects and antioxidant levels and other biochemical factors. Materials and Methods: In this study, 24 rats were evenly distributed into 4 groups, each group comprising 6 rats. Group 1 cocedered control, Group 2 administered 1000 mg/kg of spirulina, Group 3 was administered 100 mg/kg of gentamicin I M. Group 4 was subjected to the same dosages and treatment methods as G2 and G3, with a 5-day course of Gentamicin and a 12-day course of spirulina. Results: Gentamicin group recorded significantly increase in Alanine aminotransferase, Aspartate transaminase, Creatinine, and Urea concentrations. The group given spirulina following gentamicin treatment had lower levels of liver and kidney enzymes than the group given gentamicin alone and there was also an increase in the glutathione, as well as a drop in malondialdehyde levels. In the histopathological analysis, the Gentamicin-treated group exhibited coagulative necrosis also vacuolar degeneration in liver cells, along with central vein congestion. In the kidneys, this group displayed glomeruli atrophy, dilatation of the Bowman's space, the presence of hyaline casts in tubules of renal, with coagulative necrosis of epithelial cells lining renal tubule, when Gentamicin combined with Spirulina, the liver section revealed intact hepatocytes. In the kidney section of the same group, glomeruli remained intact, with only mild cell swelling observed in the epithelial cells lining the tubules of renal. Conclusion: spirulina has beneficial effects in the liver and kidneys of rats given gentamicin. [ABSTRACT FROM AUTHOR]