Background: There is a relatively high prevalence of liver illnesses since the liver is one of the organs most prone to be harmed by interaction with xenobiotics (drugs, alcohol, drug misuse, environmental pollutants, and others). Worldwide and in India, high death rates are associated with cirrhosis, fatty liver, chronic hepatitis, and cancer. One of the most prevalent malignant diseases in humans and the second greatest cause of cancer-related death worldwide, liver cancer is a serious issue, particularly in less developed areas. Different experimental models have been developed to ascertain the mechanisms by which liver lesions arise in light of the rising frequency of liver illnesses. The plant species in the genus Leonotis and family Lamiaceae known as Leonotis nepetifolia, commonly called Klip dagga, Christmas candlestick, or lion's ear, has a variety of pharmacological effects. Method: The primary LNR compounds were docked against the Caspase-3 enzyme using computational methods in the current experiment. The Auto Dock software used a grid-based docking algorithm to determine the bond. Using the Merck Molecular Force Field, 2D structures of compounds were created, transformed to 3D, and then energetically decreased up to an arms gradient of 0.01. (MMFF). Results: LNR found to be effective hepatoprotective agent and their lead molecules effectively binds to be target protein caspase-3 enzyme with binding energy -4.92 & -4.09 kcalmol-1 for chlorogenic acid & gallic acid respectively. Conclusion: A computationally based docking investigation revealed that both lead compound (chlorogenic acid and gallic acid) has potent caspase-3 inhibitory properties. Both compounds have same covalent interaction at Phe128 & Met61. The outcomes showed a promising docking score and a pattern of strong covalent interaction between the lead chemical and the target protein's active region. Gallic acid and chlorogenic acid work together synergistically to induce hepatoprotection in the ethanolic root extract from L. nepetaefolia.