Liver and kidneys disorders are fundamental public health problems as they are critical to exogenous substances such as natural poisons and/or medications that eventually lead to various hepatic and renal disorders mostly due to interference with oxygen metabolism. This study was carried out to evaluate the impact of the sugarcane peel extract on hepatic and renal complications linked to toxicity. Forty Sprague Dawley male rats (150-180g), equally divided into four equal groups. On 13th day of the experiment, the group I and II received distilled water and a single dose of paracetamol (3g/kg bwt), respectively. Group III pretreated with Saccharum officinarum peel extract (SOPE) at 200mg/rat for 13 days plus paracetamol (3g/kg bwt) on the 13th day before 1hr of treatment and group IV rats received pretreatment with Silymarin at 0.3g/kg bwt for successive 13 days plus paracetamol (3g/kg bwt) on the 13th day before 1hr of treatment. At the end of the trial, biochemical parameters besides liver and kidney histopathology were examined. Results revealed that the toxin group with a single overdose of paracetamol caused a critical increase in liver enzymes and kidney markers, bilirubin, alkaline phosphatase, lipid levels, an increase in C-reactive protein values, and caused decreases in serum levels of albumin, total protein, oxidative stress parameters (CAT, SOD, and GSH). On the other hand, co-administration of (SOPE) pretreatment showed an impact in minimizing and preventing all of these risks represented in avoiding liver and kidney damage resulting from some medication overdoses. In conclusion, the possible mechanism of protective activity of Saccharum officinarum peels extract is owing to its antioxidant and anti-inflammatory effect.