G-quadruplex (G4) is a unique nucleic acid structure that formed when a four-stranded structure is produced within a single-stranded guanine-rich sequence. Four guanine molecules form a square planar arrangement, termed G-quartet, which are stacked on top of each other to form the G4 structure in DNA (G4DNA) and in RNA (G4RNA). Recent studies have revealed that G4DNA and G4RNA are folded in cells, which suggested their biological and pharmacological significance in DNA replication, transcription, epigenetic modification, and RNA metabolism. So far, we have reported the following; 1) G4 is a target of cognitive function therapy for ATR-X intellectual disability syndrome, in which mutations are found in a G4 binding protein ATRX. 2) G4 is formed in heterochromatin depending on neuronal development. 3) G4 promotes prionoids in a CGG triplet repeat disease, Fragile X-associated tremor/ataxia syndrome (FXTAS). 4) 5-aminolevulinic acid is a potential candidate drug for treating some neurological diseases through the G4 binding ability. In this review, we summarized the significant roles of G4 in neurological diseases.