It has been suggested that altered levels/function of brain-derived neurotrophic factor (BDNF) play a role in the pathophysiology of neurodegenerative diseases including Alzheimer’s disease. BDNF positively contributes to neural survival and synapse maintenance via stimulating its high afifnity receptor TrkB, making upregulation of BDNF and/or activation of BDNF-related intracellular signaling an attractive approach to treating neurodegenerative diseases. In this short review, I brielfy introduce small natural compounds such as lfavonoids that successfully increase activation of the BDNF system and discuss their beneifcial effects against neurodegeneration.