Due　to　the　increased　crewed　spaceflights　in　recent　years,　it　is　vital　to　understand　how　the　space　environment　affects　human　health.　A　lack　of　gravitational　force　is　known　to　risk　multiple　physiological　functions　of　astronauts,　particularly　damage　to　the　central　nervous　system　(CNS).　As　innate　immune　cells　of　the　CNS,　microglia　can　transition　from　a　quiescent　state　to　a　pathological　state,　releasing　pro-inflammatory　cytokines　that　contribute　to　neuroinflammation.　There　are　reports　indicating　that　microglia　can　be　activated　by　simulating　microgravity　or　exposure　to　galactic　cosmic　rays　(GCR).　Consequently,　microglia　may　play　a　role　in　the　development　of　neuroinflammation　during　spaceflight.　Prolonged　spaceflight　sessions　raise　concerns　about　the　chronic　activation　of　microglia,　which　could　give　rise　to　various　neurological　disorders,　posing　concealed　risks　to　the　neural　health　of　astronauts.　This　review　summarizes　the　risks　associated　with　neural　health　owing　to　microglial　activation　and　explores　the　stressors　that　trigger　microglial　activation　in　the　space　environment.　These　stressors　include　GCR,　microgravity,　and　exposure　to　isolation　and　stress.　Of　particular　focus　is　the　activation　of　microglia　under　microgravity　conditions,　along　with　the　proposal　of　a　potential　mechanism.