Bidens pilosa is generally used as ethnomedicine and functional food worldwide. We have reported previously that Miyako Island Bidens pilosa extract (MBP) suppresses glial activation and prolongs the life span in the SOD1G93A transgenic mouse model of Amyotrophic Lateral Sclerosis (G93A). However, the therapeutic mechanisms of MBP remain unclear. In the present study, we investigated the microglia activation and polarization profile in the spinal cord of G93A. Real-time PCR revealed that oral administration of MBP at 2 g/kg/day for 7 days was inhibited the induction of M1-microglial markers (CD11c, IFN-γR) and inflammatory cytokines (TNF-α, IL-1β, IL-6). In contrast, the increased expression of M2-microglial markers (IL-13R, Ym1) and anti-inflammatory cytokines (TGF-β, IL-10) was not affected. Moreover, we determined the effect of MBP on cell proliferation using BV2 microglia cell line. Exposure of BV2 cells to MBP, resulted in a reduction of MTT reduction activity without increase the number of ethidium homodimer-1 stained dead cells. We also found that MBP suppressed the LPS-induced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) production. These results suggest that MBP regulates neuroinflammation through suppressing the microglia polarizing into M1 type.