To investigate the protective effects of bilirubin on white matter injury and cognitive impairment under chronic cerebral hypoperfusion, and to elucidate its association with the regulation of microglial functional states. Methods: A bilateral common carotid artery stenosis (BCAS) mouse model was employed to induce chronic cerebral hypoperfusion. Behavioral assessments, histological analyses, and single-cell transcriptomic profiling were integrated to systematically evaluate the effects of bilirubin on white matter integrity and the inflammatory microenvironment. Results: Bilirubin treatment significantly improved learning, memory, and recognition abilities in BCAS mice, accompanied by marked attenuation of demyelination and structural disruption in the corpus callosum. Single-cell transcriptomic and histological analyses revealed that bilirubin suppressed inflammatory and immune-response-related transcriptional programs, thereby inhibiting the inflammatory and phagocytic activation of microglia. Trajectory inference and transcription factor regulatory analyses demonstrated that bilirubin redirected microglial state transitions away from inflammation-associated terminal states toward homeostatic and repair-related phenotypes. This shift was characterized by enhanced TGF-β-associated regulatory networks and concurrent suppression of interferon signaling pathways. Conclusion: Bilirubin effectively alleviates white matter injury and cognitive dysfunction induced by chronic cerebral hypoperfusion by reshaping microglial functional states and the inflammatory microenvironment.