The bio activation of drugs to chemically active compounds, induces liver injury resulting in various degenerative diseases, which could be overcome by the administration of sulphated polysaccharides. The present study addresses, the hepatoprotective potential of crude sulphated polysaccharides (CSP) from Turbinaria ornata using a Swiss albino rat model where liver damage was induced with Rifampicin (RMP) and Isoniazid (INH). The RMP-INH (75 mg/kg body weight) and CSP (10, 25, 50 and 200 mg/kg body weight) were orally administered to Swiss albino rat for 14 days. Silymarin (100 mg/kg body weight) administered group served as a positive control. At the end of the experiment serum was collected and the rats were dissected and the organs like liver, kidney and brain were collected. Administration of hepatotoxin causes increase in serum SGPT, SGOT, lipid peroxidation levels and a decrease in reduced glutathione, GST levels. Co-administration of CSP shows hepatoprotective activity on hepatotoxin induced damage. The hepatoprotective activity was also supported by histopathological studies of liver sections. In addition, our study revealed that the effect of toxicity induced in liver also caused damage to kidney and brain tissues resulting in decrease of total antioxidant status, reduced glutathione, increased levels of nitrate and macromolecular damage like lipid peroxidation. Co-administration of CSP significantly prevents the damage of liver, kidney and brain caused by hepatotoxin. The CSP (25 mg/kg body weight) from T. ornata could be a better hepatoprotective agent than standard drug Silymarin.