Background <p>Neuroinflammation is a common consequence of intracerebral hemorrhage (ICH), leading to neurological impairments. Research indicates that the gut microbiome can influence neuroinflammatory responses. Erianin, is a potential therapeutic agent in the treatment of inflammation. Yet, the specific impact of erianin on ICH-induced inflammation and its interaction with the gut microbiome remain areas of ongoing investigation.</p> Methods <p>ICH mouse model was established and treated with erianin. Neurobehavioral tests, brain water content, immunofluorescence, western blotting, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed to measure the neurological defects and neuroinflammation and neuron apoptosis. Immunofluorescent staining and western blotting assay were performed to assess the activation states of microglia and inflammation. The quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and FITC-dextran assays were utilized to measure the intestinal barrier integrity. The composition of the gut microbiota was analyzed by sequencing the 16&#xa0;S rRNA extracted from fecal samples.</p> Results <p>Administration of Erianin notably decreased inflammation in the brain and improved neurological function in ICH mice by inhibiting the proinflammatory activation of microglia. Additionally, Erianin bolstered intestinal barrier integrity, evidenced by decreased levels of lipopolysaccharide-binding protein. Furthermore, treatment with Erianin led to observable shifts in the gut microbiota. Notably, the activation of the ERK signaling pathway was found to counteract the neuroprotective effects of Erianin following ICH.</p> Conclusions <p>Erianin is a therapeutic candidate for addressing neuroinflammation triggered by ICH, with its mechanisms of action likely involving the modulation of ERK signaling and the gut microbiome.</p>