The invention relates to pharmaceutical compositions and applications thereof, and a pharmaceutical preparation. The invention provides various novel compositions of berberine in combination with pharmacologically active EPA and DHA, and related methods of their use in treating various diseases or disorders. The pharmaceutical compositions of the invention are useful in treating and / or preventing various diseases or disorders, including metabolic diseases or disorders such as dyslipidemia, hyperglycemia, hypertriglyceridemia, hyperlipidemia, diabetic dyslipidemia, diabetic hyperlipidemia, dyslipidemia in statin-intolerance patients, diabetes, diabetic complications, hypercholesterolemia, or obesity. Additionally, the pharmaceutical compositions of the invention are useful in treating and / or preventing atherosclerosis, heart diseases, neurodegenerative diseases, inflammation, cancers, as well as various liver diseases or disorders, such as fatty liver, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cholestatic liver diseases or graft-versus-host disease of the liver. Furthermore, the pharmaceutical compositions of the invention are useful in improving liver functions in chronic viral associated liver diseases and alcohol-related liver diseases.