Metabolic disorders, including type 2 diabetes and obesity, represent major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK has been demonstrated to mediate, at least in part, the effects of a number of physiological and pharmacological factors that exert beneficial effects on these disorders. Thus, the identification of a compound that activates the AMPK pathway would contribute significantly to the treatment and management of such syndromes. In service of this goal, we have screened a variety of naturally occurring compounds and have identified one compound, cryptotanshinone, as a novel AMPK pathway activator. Cryptotanshinone was originally isolated from the dried roots of Salvia militorrhiza, an herb that is used extensively in Asian medicine and that is known to exert beneficial effects on the circulatory system. For the first time, in the present study, we have described the potent antidiabetic and antiobesity effects of cryptotanshinone, both in vitro and in vivo. Our findings suggest that the activation of the AMPK pathway might contribute to the development of novel therapeutic approaches for the treatment of metabolic disorders such as type 2 diabetes and obesity.