The objective of the current investigation was to investigate the hepatoprotective effect of Polyherbal Acetonic extract of Curcuma longa rhizome and Sida spinosa leaves extracts against carbon tetrachloride (CCl4)-induced liver injury in rats. The Polyherbal Acetonic extract of Curcuma longa rhizome and Sida spinosa leaves were administered orally at a dosage of 150, 300 and 500 mg/kg body weight to Wistar albino rats, with Silymarin serving as the standard. Polyherbal Acetonic extract extract showed a strong hepatoprotective effect by restoration of functional parameters, physical parameters, biochemical parameters and reducing blood enzymes alkaline phosphatase (ALP), and total bilirubin (TBL) in the chosen animal. The chemical contents of the plant include alkaloids, flavonoids, glycosides, steroids, terpenoids, phenolics, and saponins, among others. The overall experimental findings imply that bioactive phytoconstituents, such as flavonoids and alkaloids found in the Polyherbal Acetonic extract of Curcuma longa rhizome and Sida spinosa leaves, may be responsible for the plant's substantial hepatoprotective action. Consequently, the findings support the use of Curcuma longa rhizome and Sida spinosa leaves as a hepatoprotective agent.