A composition, and an application and pharmaceutical preparation thereof. The invention provides a plurality of novel compositions and preparations comprising a berberine in combination with EPA and DHA, and an application thereof for treating a plurality of diseases. The composition is used for treating, alleviating, or preventing a plurality of diseases or disorders including metabolic diseases or disorders such as dyslipidemia, hyperglycemia, hypertriglyceridemia, hyperlipidemia, diabetic dyslipidemia, diabetic hyperlipidemia, hyperlipidemia in a statin-intolerant patient, diabetes, hypercholesterolemia complications of diabetes, or obesity. The composition can also be used for treating and/or preventing atherosclerosis, heart disease, neurodegenerative disease, inflammation, cancer, and a plurality of liver diseases or disorders such as fatty liver, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cholestatic liver disease, or hepatic graft-versus-host disease. In addition, the composition can be used to improve liver functions in chronic viral hepatitis and alcoholic liver disease.