This study was designed to evaluate the neuroprotective effects of Morinda citrifolia L. (Rubiaceae), commonly known as noni, and memantine (a N-methy-D-aspartate receptor inhibitor) on hydrocephalus-induced neurodegenerative disorders. Kaolin was injected into the cistern magna of male adult New Zealand rabbits to establish a hydrocephalus animal model. Memantine (20 mg/kg, intraperitoneally; memantine-treated group) or noni (5 mL/kg, intragastrically; noni-treated group) was administered daily for 2 weeks. Microtubule-associated protein-2 and caspase-3 immunohistochemistry were performed to detect neuronal degeneration and apoptosis in the periventricular tissue of the fourth ventricle of rabbits. Microtubule-associated protein-2 staining density was significantly decreased in the hydrocephalic group, while the staining density was significantly increased in the memantine- and noni-treated groups, especially in the noni-treated group. Noni treatment decreased the number of caspase-3-positive cells in rabbits with hydrocephalus, while memantine had no effect. These findings suggest that noni exhibits more obvious inhibitory effects on hydrocephalus-induced neurodegenerative disorders than memantine in periventricular tissue of the fourth ventricle. This study was designed to evaluate the neuroprotective effects of Morinda citrifolia L. (Rubiaceae), commonly known as noni, and memantine (a N-methy-D-aspartate receptor inhibitor) on hydrocephalus-induced neurodegenerative disorders. Kaolin was injected into the cistern Magna of male adult New Zealand rabbits to establish a hydrocephalus animal model. Memantine (20 mg / kg, intraperitoneally; memantine-treated group) or noni (5 mL / kg, intragastrically; Microtubule-associated protein-2 and caspase-3 immunohistochemistry were performed to detect neuronal degeneration and apoptosis in the periventricular tissue of the fourth ventricle of rabbits. Microtubule-associated protein-2 staining was significantly less in the hydrocephalic group, while the staining density was significantly increased in the memantine- and noni-treated groups, especially in the noni-treated group. Noni treatment decreased the number of caspase-3- positive cells in rabbits with hydrocephalus, while memantine had no effect. These findings suggest that noni exhibits more obvious inhibitory effects on hydrocephalus-induced neurodegenerative disorders than memantine in periventricular tissue of the fourth ventricle.