Naturally occurring small molecules from plants, microorganisms, and animals allow the design of drugs that can be beneficial in virtually all kinds of human diseases. Liver diseases with diverse etiologies such as viral infection, chemical intoxication, and metabolic fat accumulation are one of the leading causes of human mortality. Unfortunately, however, there are few effective drugs available capable of stopping or reversing the progress of liver disease. Here, we discuss the current advances in developing hepatoprotective natural products for several arrays of liver disease pathogenesis.