Abstract: Background and Objective: Research on liver diseases have been on increase and have become a global concern. Cucumis sativus has been reported to have anti-oxidant activity, high flavonoid content, anti-inflammatory and analgesic activity and may likely of help in the management of liver disease. The hepatoprotective effect of the homogenate of Cucumis sativus fruit were therefore studied and histopathological assessment of the liver damage was done. Materials and Methods: The fresh fruit of Cucumis sativus was homogenized and used for all experimental analysis. The effects of the fruit homogenate on liver function biomarkers and lipid profile in rats intoxicated with carbon tetrachloride (CCl4) were evaluated using standard biochemical methods. Data were analyzed using SPSS and two-way ANOVA; the acceptance level of significance was p<0.05. Results: Treatment of rats with the homogenate of Cucumis sativus fruits significantly (p<0.05) decreased CCl4-induced elevated levels of the liver enzymes and total bilirubin in the serum when compared to positive control. The homogenate also attenuated the CCl4-induced elevation of LDL, total cholesterol and triacylglycerol concentration and ameliorated the induced depletion of HDL. Pre-treatment with Cucumis sativus fruit homogenate significantly improved the structure of hepatic cells. The homogenate showed a sign of liver cell protection comparable to that of the standard drug-silymarin. Conclusion: The results of this study demonstrated that the homogenate was effective in the prevention of CCl4-induced hepatic damage in rats and may improve the liver integrity of consumers.