Methysticin is a kavalactone originally found in Piper methysticum (kava plant). Methysticin exhibits neuroprotective, neuromodulatory, and antifungal activities. Methysticin may also display anti-inflammatory benefit, inhibiting activation of NF-κB in lung adenocarcinoma tissue. Methysticin activates Nrf2 in neurons and astroglia, protecting against amyloid-β (Aβ)-induced neurotoxicity. This compound displays antimicrobial efficacy against species of Fusarium, Trichoderma, and Colletotrichum. Additionally, methysticin inhibits peak amplitude of voltage-gated Na+ channels in hippocampal neurons. Methysticin administration activates the Nrf2 pathway and reduces neuroinflammation, hippocampal oxidative damage and memory loss in a mouse model of AD. Therefore, kavalactones might be suitable candidates to serve as lead compounds for the development of a new class of neuroprotective drugs.