The　neuroprotective　role　of　sodium-glucose　cotransporter-2　inhibitor　(SGLT2i)　has　attracted　considerable　interest.　The　purpose　of　this　study　was　to　investigate　the　role　of　SGLT2i　in　several　common　neurodegenerative　diseases　(NDs),　including　Alzheimer＇s　disease　(AD),　Parkinson＇s　disease　(PD),　amyotrophic　lateral　sclerosis　(ALS),　and　multiple　sclerosis　(MS).　Utilizing　drug-target　Mendelian　randomization　(MR)　and　colocalization,　we　used　single　nucleotide　polymorphisms　(SNPs)　proximal　to　the　SLC5A2　gene　to　analyze　the　influence　of　SGLT2i　on　AD,　PD,　ALS,　and　MS.　Sensitivity　analyses　were　performed　to　assess　heterogeneity　and　pleiotropy.　Phenome-wide　association　study　(PheWAS)　was　used　to　probe　the　relationship　of　SGLT2i　with　other　characteristics.　Protein-protein　interaction　(PPI)　networks　were　used　to　explore　how　SLC5A2　affects　other　proteins,　and　enrichment　analysis　was　used　to　explore　possible　biological　processes.　The　MR　analysis　showed　that　SGLT2i　was　negatively　associated　with　AD　(OR　=　0.77,　p　=　0.01),　PD　(OR　=　0.52,　p　=　0.04),　ALS　(OR　=　0.60,　p　=　0.01),　and　MS　(OR　=　0.33,　p　=　0.027),　indicating　that　SGLT2i　could　reduce　the　risk　of　AD　by　23%,　PD　by　48%,　ALS　by　40%,　and　MS　by　67%.　The　colocalization　supported　this　conclusion.　The　PheWAS　showed　that　SGLT2i　was　associated　with　body　mass　index　and　systolic　blood　pressure.　SGLT2i　is　biologically　closely　related　to　the　development　of　NDs.　This　study　suggested　that　SGLT2i　was　able　to　reduce　the　risk　of　NDs.　SGLT2i　may　perform　this　process　through　many　mechanisms.　This　study　provides　a　new　perspective　on　the　treatment　of　NDs;　clinical　trials　and　relevant　experiments　are　necessary　to　further　validate　the　neuroprotective　effects　of　SGLT2i.