The aim of the present study was to evaluate the protective effect of Syzygium cymosum leaf methanol extract (SCL) against carbofuran (CF)-induced hepatotoxicity in Sprague-Dawley rats, along with the identification and quantification of polyphenolic composition by high-performance liquid chromatography (HPLC). Results revealed the presence of alkaloids, tannins, and flavonoids in SCL. Similarly, HPLC analysis suggests that SCL contains some known important antioxidants, such as rutin, benzoic acid, and salicylic acid that could be responsible for the hepatoprotective activity of the extract. In CF-exposed rats, significant hematological alterations along with histological changes were marked by the presence of necrosis, congestion, and inflammation. CF-intoxication also showed an increase in lipid peroxidation and decrease in cellular antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) levels in rats compared with the control group. Furthermore, coadministration of SCL significantly ameliorated the abnormalities and improved the cellular arrangement in experimental animals. SCL also reversed the alteration of hematological and biochemical parameters and brought them back to normal levels as compared to the control group. In conclusion, S. cymosum may be one of the best sources of natural antioxidant compounds that can be used in the treatment of oxidative stress and stress-related diseases and disorders.