| Summary: | <i>Ganoderma lucidum</i> (<i>G. lucidum</i>) has been widely used for its health benefits as an edible and traditional medicinal mushroom for thousands of years in Asian countries. It is currently used as a nutraceutical and functional food owing to its major bioactive compounds, polysaccharides and triterpenoids. <i>G. lucidum</i> exhibits a broad range of hepatoprotective impacts in various liver disorders, such as hepatic cancer, nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease, hepatitis B, hepatic fibrosis, and liver injury induced by carbon tetrachloride (CCl4) and α-amanitin. <i>G. lucidum</i> protects the liver through a broad range of mechanisms that include the modulation of liver Phase I and II enzymes, the suppression of β-glucuronidase, antifibrotic and antiviral actions, the regulation of the production of nitric oxide (NO), the maintenance of hepatocellular calcium homeostasis, immunomodulatory activity, and scavenging free radicals. <i>G. lucidum</i> could signify an encouraging approach for the management of various chronic hepatopathies, and its potential mechanisms make it a distinctive agent when used alone or with other drugs and applied as a functional food, nutraceutical supplement, or adjuvant to modern medicine. This review summarizes the hepatoprotective properties of <i>G. lucidum</i> with its various mechanisms of action on different liver ailments. Biologically active substances derived from <i>G. lucidum</i> are still being studied for their potential benefits in treating different liver ailments.
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