An oligosaccharide fraction isolated from the mycelium of the Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (GLOS) was separated by size-exclusion chromatography. The chemical structure of GLOS consists of a disaccharide repeating unit [-4-b-1-Galf(1-6)-O-(β-Glcp)−1-]n (n=3,4). In addition, this study was undertaken to determine the possible anticonvulsant and neuroprotective effects of GLOS (10–80 mg/kg) on kainic acid (KA)-induced seizures. The behavioral alterations and histopathology of hippocampal neurons were studied. Our results show that GLOS inhibited convulsions in rats from KA-induced seizures, reduced the degeneration pattern in the CA3 region of rats, decreased astrocytic reactivity, and reduced the expression of IL-1β and TNF-a induced by KA. These results indicate a potential anticonvulsant and neuroprotective effects of GLOS.