Objective: The purpose of our study was to examine whether administration of aqueous extract of the leaves of Ocimum sanctum L. (Tulsi) do possess a protective effect against cadmium-induced oxidative stress in rat liver. Methods: Male albino rats were divided into four groups; control, cadmium treated, aqueous extract protected and only aqueous extract treated (positive control). The rats were treated with cadmium chloride subcutaneously every alternate day for a period of fifteen days and the extract was administered orally every day for fifteen days. The alterations in the activity of the different bio-markers of hepatic damage, biomarkers of oxidative stress, activities of the antioxidant, pro-oxidant enzymes and some of the mitochondrial enzymes were studied. Histomorphology and alteration in tissue collagen level was studied through H-E staining and Sirius red staining respectively. Quantification of tissue collagen content was evaluated using confocal microscopy. Result: The studies revealed that the Tulsi leaf aqueous extract protected the biomarkers of organ damage, oxidative stress, antioxidant enzymes, pro-oxidant enzymes, mitochondrial respiratory chain enzymes, enzymes of electron transport chain and oxidative stress index from getting altered in the rat liver tissue following treatment with cadmium chloride. Conclusion: The current work suggests that the Tulsi leaf aqueous extract may be useful as a protective antioxidant supplement with promising antioxidant potential to combat cadmium-induced oxidative damages in the hepatic tissue.