Background: Ocimum sanctum (OS) Linn. commonly known as Holy Basil or Tulsi is an Ayurvedic herb of India. The culinary, medicinal, and industrial importance of this plant led to explore its chemical and pharmacological properties. Objective: The present study was carried out to know the anti-oxidant activity of carvacrol bioactive compound of OS in sodium fluoride (NaF) rats and free-radical scavenging activities of OS. Materials and Methods: Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione (GSH), GSH-s-transferase (GST), malonaldehyde (MDA), alanine aminotransferase (AAT), aspartate aminotransferase (AST), alkaline phosphatase (ALKP), calcium (Ca), and phosphorus (P4) levels are estimated in all experimental groups. 2,2-Diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), and hydroxyl radical activities are analyzed in the ethanolic extract of OS. Results: SOD, CAT, GPx, GR, GSH, activities, and Ca levels depleted and GST, MDA, AAT, AST, ALKP, and P4 levels elevated in NaF intoxicated rats. Whereas carvacrol supplementation normalized all the antioxidant enzymes and hepatic markers in NaF toxicity rats. DPPH, H2O2, and hydroxyl radical of OS showed potent free-radical scavenging activities. In addition, histopathological studies also prove that carvacrol protected the liver tissue from fluoride toxicity in rats. Conclusion: The present study revealed that carvacrol of OS modulated the antioxidant enzymes and hepatic stress markers in NaF rats. Our research study will be helpful in the development of new active principle and nutraceuticals in the area of drug resistance and therapeutic compounds against disease vectors.