Saponarin (SA), a natural flavonoid, is known for its antioxidant and hepatoprotective activities. Saponarin is found in diverse plants, including Tinospora cordifolia, which is used in an anti-diabetic drug, Aloe barbadensis, and barley leaves.Saponarin, isolated from Gypsophila trichotoma Wend., showed in vitro and in vivo hepatoprotective and antioxidant activity against CCl₄-induced liver damage. Saponarin pretreatment also decreased cocaine toxicity both by increasing GSH levels and antioxidant enzyme activities. SA isolated from barley sprouts exerts anti-inflammatory effects in LPS-induced RAW 264.7 macrophages via inhibition of NF-κB, ERK and p38 signaling. Thus, SA may be a promising natural anti-inflammatory agent. Saponarin improves gluconeogenesis and glucose uptake. Saponarin regulates AMPK through induction of intracellular calcium levels. Saponarin has a hypoglycemic effect through the activation of the AMMKb–AMPK–CREB signaling axis in hepatocytes.