Niclosamide is an anthelmintic that disrupts mitochondrial metabolism in parasitic worms and animal models. It inhibits STAT3 (IC50 = 0.25 μM) and stimulates autophagy by reversibly inhibiting mammalian target of rapamycin complex 1 (mTORC1) signaling. It completely inhibits phosphorylation of ribosomal S6 kinases (S6K) when used at a concentration of 3 µM. Niclosamide (1 µM) induces mitochondrial uncoupling, decreasing cellular ATP concentrations and increasing the ratio of ADP to ATP in HepG2 cells, and activates AMP-activated protein kinase (AMPK) in NIH3T3 cells. It also increases lipid oxidation by 5-fold in HepG2 cells. It prevents high-fat diet-induced hepatic steatosis and insulin resistance and improves glycemic control in db/db mice when administered at a dose of at 125 mg/kg per day. Niclosamide also inhibits proliferation and colony formation of DU145 prostate cancer cells, which have constitutively active STAT3 (IC50s = 0.7 and 0.1 µM, respectively).