The first description of the medical use of licorice appeared in“Shennong Bencao Jing”,one of the well-known Chinese herbal medicine classic books dated back to 220-280 AD.As one of the most commonly prescribed Chinese herbal medicine,licorice is known as“Guo Lao”,meaning“a national treasure”in China.Modern pharmacological investigations have confirmed that licorice possesses a number of biological activities,such as antioxidation,anti-inflammatory,antiviral,immune regulation,and liver protection.18β-glycyrrhetinic acid is one of the most extensively studied active integrants of licorice.Here,we provide an overview of the protective effects of 18β-glycyrrhetinic acid against various acute and chronic liver diseases observed in experimental models,and summarize its pharmacological effects and potential toxic/side effects at higher doses.We also make additional comments on the important areas that may warrant further research to support appropriate clinical applications of 18β-glycyrrhetinic acid and avoid potential risks.