Introduction: Silymarine extract is currently prescribed by some physicians for treatment of fatty liver disease. In the present study, the effect of administration of tablet containing silymarine extract on plasma homocysteine (Hcy), folate, vitamin B12 and liver enzymes activity in non-alcoholic steatohepatitis (NASH) was investigated. Materials and Methods: Seventy-four patients (40 female and 34 male aged 32-44 years) who were diagnosed with NASH and hyperhomocysteinemic by liver biopsy, measurement of liver enzymes activity and plasma Hcy were recruited for this study. The patients were not consuming alcohol or taking any other medications/medicines. Plasma Hcy, folate, B12, cholesterol, triglyceride, fasting glucose, aspartate aminotransferase (AST) and alaninaminotransferase (ALT) activity of all patients were measured before and after treatment. Tablet containing silymarine extract (140mg∕kg) was administrated thrice /three times a day for 2 months. Results: The results showed a significant reduction in the level of plasma Hcy, cholesterol, triglyceride, fasting glucose (P <0.05) following the administration of tablet containing silymarine extract, however, the increase in plasma folate and B12 levels was not significant. The results did not demonstrate any significant negative correlations between Hcy and B12, and also between Hcy and folate. Conclusion: It can be concluded that consumption of tablet containing silymarine extract in NASH patients significantly reduces level of plasma Hcy, cholesterol, triglyceride, fasting glucose and AST and ALT activity, while level of plasma folate and B12 remained unchanged.