Isorhamnetin, a flavonol aglycone, isolated from the traditional Chinese medicine H. rhamnoides L., was frequently used in traditional medicine to prevent and treat diverse diseases. Isorhamnetin has been shown to play a variety of roles in anti-oxidation, anti-inflammation, anti-tumor, anti-viral, and neurodegenerative injury protection. Isorhamnetin could inhibit the H2O2-induced activation of the intrinsic apoptotic pathway by scavenging free ROS and extracellular signal-regulated kinase 1/2 (ERK1/2) inactivation. In the type 2 diabetic rat model, isorhamnetin was found to be able to inhibit the NF-κB signaling activity, attenuate oxidative stress, and decrease the production of inflammatory mediators. Isorhamnetin can suppress skin cancer, breast cancer, colon cancer and atherosclerosis by inhibiting PI3K/AKT activation. Isorhamnetin shows inhibitory activity toward CYP1B1 expression and function.