Hepatotoxicity is the major health problem that is a global concern worldwide especially Egyptian people because the liver injury is one of the most ten disease leading to death. There are many factors leading to hepatotoxicity as antibiotics which topping the list of agents that cause drug induced liver injury especially Isoniazid (INH) and rifampicin (RIF) which are the first line remedies in treatment of tuberculosis but they are associated with hepatotoxicity. The present study evaluates the possible hepatoprotective effects of Solanum nigrum,and Moringa oleifera against the experimentally induced hepatotoxicity with INH/RFP in rats. Seventy two rats (200-250g) were allocated into nine groups (8 rats in each group), and treated as follow: group I, received normal saline orally; group II, received INH/RFP (50 mg/Kg/day of each) for 28 days orally; group III, received Silymarin (50 mg/kg/day) + INH/RFP for 28 days orally; group IV, received of Solanum nigrum methanolic extract(SNME) (250 mg/Kg/day) + INH/RFP for 28 days orally; group V, received SNME (500 mg/Kg/day) + INH/RFP; group VI, received SNME (1000 mg/Kg/day) + INH/RFP; group VII, received Moringa oleifera ethanolic extract (MOEE) (250 mg/Kg/day) + INH/RFP for 28 days, VIII, received MOEE (500mg/Kg/day) + INH/RFP for 28 days while IX, received MOEE (1000mg/Kg/day) + INH/RFP for 28 days. Co-administration of herbal plants with INH/RFP reduced elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and (bilirubin total &direct) levels but also elevated malondialdehyde (MDA) & tumor necrosis factor-α (TNF-α) contents in liver homogenate. Moreover, they reduced glutathione peroxidase (GPX) & Adiponectin activity. Microscopic examination showed diffuse hepatocellular steatosis, mononuclear inflammatory cells infiltration, abundant apoptosis and large focal area of hepatocellular necrosis. But when silymarin administered to rat’s histopathological figure revealed minimal reduction in the severity of the liver damage as shown vacuolar degeneration of hepatocytes associated with sporadic cell necrosis. Solanum nigrum administration to rats, in present study, led to remarkablepreservation in their histological profile especially high dose (1000mg/kg) as compared with hepatotoxic group where histopathological examination revealed that high dose solanum pretreated rats showing apparently normal hepatocytes with increased number of binucleated cells. Moreover, Moringa olifera extract administration to rats showing individual cell necrosis of the periportal hepatocytes in histopathological examination. It is concluded that Solanum nigrum and or Moringa olifera might be considered as adjuvant drug in treatment of liver disorder and or as hepatoprotective therapy with anti-tubercular drugs.