This study was aimed to evaluate the hepatoprotective and antioxidant potential of the total alkaloid fraction of Polyalthiya longifolia fruits (TAFPL) by in-vitro and in-vivo methods. In the in-vitro study,Primary rat hepatocytes and HepG2 cells were exposed with CCl4 along with/without various concentrations of TAFPL (50,100,200 µg/kg) and the effects were studiedIn-vivo studies, CCl4 intoxication method was used and aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), total bilirubin and total proteins were estimated and supported with histopathological studies. TAFPL (50,100,200 µg/kg) treated animals showed dose dependant protective activity in terms of increased percentage of viability against CCl4 intoxication in both primary hepatocytes (p<0.001) and in HepG2 cells (p<0.01). TAFPL at the doses of (100 and 200 mg/kg) produced significant hepatoprotective effect by decreasing the elevated serum enzymes, bilirubin, LPO and significantly increased the levels of glutathione (GSH), catalyse (CAT) and super oxide dismutase (SOD). Additionally, in-vitro antioxidant studies revealed that TAFPL scavenged free radicals and maximum percentage inhibition of DPPH was 57% at 200µg/mL whereas in nitric oxide radical scavenging model,inhibition is about 51% at 200µg/mL and in reducing power method,TAFPL demonstrated dose dependent antioxidant activity comparable with ascorbic acid. Addtionally, treatment with TAFPL fruits showed a dose dependent reversal of histopathological changes induced by CCl4. Based on the results, it was concluded that, TAFPL possesses hepatoprotective and antioxidant activity against CCl4 intoxication in both in-vitro and in-vivo methods through its free radical scavenging and antioxidant properties on hepatocytes.