Abstract This work investigated the antioxidant and hepatoprotective activities of lemongrass extract and its effects on rat hepatotoxicity. The lemongrass extract (LGE) contains bioactive components such as phenolic acids, flavonoid components, vitamin C, fibers, and tannins. The LGE had high phenolic content (397 mg/100g) and flavonoids (164 mg/100g), influencing its antioxidant activity of 91.25%. Additionally, it inhibited 81% of breast cancer, also, inhibited the growth of pathogenic bacteria and Candida at a concentration of 20-40 µg/mL. Additionally, it inhibited SARS-Cov-2 by 75%; however, increasing the activity of Cas-3. Quercetin-3-rhamnoside was the main phenolic compound in the HPLC profile; the phenolic compounds may be attributable to the beneficial effects of LGE. In this study, the CCl4-challenged rats delivered two levels of LGE (100 and 300 mg/kg BW). LGE reduced ALT, AST, creatinine and urea by 50 and 37%, respectively. Generally, LGE mitigated the oxidative stress induced by CCl4, which is evident in the histology of liver and kidney tissues, where significant improvement, with no cytoplasmic degradation in undamaged liver hepatocytes, improved kidney performance and shape. It can be concluded that polyphenolic-rich LGE can mitigate the oxidative stress induced by CCl4 and other parameters while enhancing kidney and liver performance.