In this study we evaluated the effect of a novel, marine-derived, acidic oligosaccharide on scopolamine-induced amnesia in rats using the Morris water maze test. The results show that 30-day administration of this oligosaccharide, referred to as acidic oligosaccharide sugar chain (AOSC), to rats attenuates memory impairment by scopolamine, as evaluated by shortened escape latency, swimming distance, and increased swimming time of rats with memory impairment induced by scopolamine in the quadrant where the platform is placed. The data additionally suggest that an appropriate dose of scopolamine, a traditional muscarinic receptor antagonist, elevates oxidative damage in brain, characterized by inactivation of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and consequently, inhibition of ATPase in the hippocampus and cerebral cortex. AOSC ameliorates oxidative injuries caused by scopolamine by increasing the activities of SOD, GSH-Px, and ATPase. Further investigation by flow cytometry revealed that AOSC significantly reduces the overloading of intracellular free calcium ion ([Ca2+]i), thus suppressing apoptosis induced by H2O2 in human neuroblastoma SH-SY5Y cells. These findings suggest that AOSC can induce cognitive improvement via its antioxidant activity.