Metformin is a biguanide drug that is commonly used as a first-line treatment for type 2 diabetes. This chemical works by activating the energy sensor AMPK that inhibits hepatic gluconeogenesis. Metformin’s therapeutic properties go beyond its use as an antidiabetic compound. As a result, a large number of publications have recently reported promising results in a variety of neurological diseases. Although several hypotheses have been formulated regarding the specific mechanisms of action of metformin in the central nervous system, such as a decrease of neuroinflammation or a reduction of oxidative stress, the underlying pathways of these positive effects remain obscure. In this chapter, we review the newly discovered benefits of metformin as a neuroprotective agent for Lafora disease, a rare form of progressive myoclonus epilepsy caused by mutations in the EPM2A or EPM2B genes. The aggregation of Lafora bodies, abnormal glycogen inclusions that accumulate in the brain and other tissues, is the major histopathological characteristic. Treatment with metformin in Lafora disease knockout mice reduced the number of Lafora bodies, decreased neuronal loss and reactive astrogliosis, and improved the functional and epileptic symptoms.