In the last years, consumers are paying much more attention to natural medicines and principles, mainly due to the general sense that natural compounds are safe. On the other hand, there is a growing demand by industry for plants used in traditional medicine that could be incorporated in foods, nutraceuticals, cosmetics, or even pharmaceuticals. Glycyrrhiza glabra Linn. belongs to the Fabaceae family and has been recognized since ancient times for its ethnopharmacological values. This plant contains different phytocompounds, such as glycyrrhizin, 18β-glycyrrhetinic acid, glabrin A and B, and isoflavones, that have demonstrated various pharmacological activities. Pharmacological experiments have demonstrated that different extracts and pure compounds from this species exhibit a broad range of biological properties, including antibacterial, anti-inflammatory, antiviral, antioxidant, and antidiabetic activities. A few toxicological studies have reported some concerns. This review addresses all those issues and focuses on the pharmacological activities reported for G. glabra. Therefore, an updated, critical, and extensive overview on the current knowledge of G. glabra composition and biological activities is provided here in order to explore its therapeutic potential and future challenges to be utilized for the formulation of new products that will contribute to human well-being.