Drug-induced liver injury is a potential complication of all medications because the liver has a central role in the metabolism of drugs and toxic substances. This study was designed to evaluate the hepatoprotective activity of the methanolic extract of Gymnema slyvestre leaves on acetaminophen-induced liver damage in wistar rats. The experiment was carried in three phases. In Phase I, the hepatoprotective activities of the methanolic extract of the leaves was determined by assaying for some liver function indices (AST, ALT & ALP) on acetaminopheninduced liver damage in rats. In phase II, the methanolic extract of the leaves was further fractionated with chloroform, ethylacetate and n-butanol to obtained chloroform, ethylacetate, n-butanol and residual extracts respectively; and the effect of these fractions on liver function (AST, ALT & ALP) was determined.