Objective: The present study was intended 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 heart. 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 cardiac 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 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 being altered in the rat tissue following treatment with cadmium chloride. Conclusion: It can be concluded from the current work that this Tulsi leaf aqueous extract may be useful as a protective antioxidant supplement with promising antioxidant potential to combat oxidative stress-induced tissue damages in the areas where humans are exposed to cadmium occupationally or environmentally.