Background: Antioxidant effect of herbal products like Silymarin & Ginger can get rid of free radicals. Nanoparticles can reach the target easily without inactivation, increase the bioavailability of the therapy and reduce its toxicity. Aim: To evaluate the protective effect of silymarin and nano-encapsulation of Ginger extract on hepatotoxicity in adult male albino rats. Materials and Methods: Eighty rats were randomized into eight groups (10 rats each). Group I (control): subdivided into 3 control subgroups; Group II: rats received nano-encapsulation of ginger extract 50 mg/kg/day by oral gavage every day. Group III: rats received 0.1 ml/100 gm/kg of Ccl4 dissolved in corn oil (1:1) twice a week by intraperitoneal injection. Group IV: Silymarin was given in a dose of 200 mg/kg/day dissolved in one ml distilled water by oral gavage every day with Ccl4. Group V: nano-encapsulation of ginger 50 mg/kg/day by oral gavage every day Ccl4. Group VI: the doses were administrated as in groups II, III &IV for six weeks in all groups. At the end of the experiment, rats were anesthetized, blood samples collected for ALT and AST measurement then sacrificed and the liver was excised, for SOD, H&E, and histoimmunological studies. Results: Ccl4-induced hepatotoxicity can be protected by silymarin or/and nano-encapsulation of ginger that showed more improvement than silymarin in histopathological and immunohistochemical, morphometric, SOD, ALT, and AST results. Conclusion: The study found that hepatotoxicity can be protected by the administration of silymarin or/and nano-encapsulation of ginger extract. Nanoencapsulation of the ginger extract showed more improvement than silymarin.