Phlorotannins (marine algal polyphenols) have been reported to exhibit beneficial biological activities, serving as both antioxidants and anti-inflammatory agents. Among marine algae, Ecklonia cava , a member of the Laminariaceae, is a very popular food regarded as healthy in Korea and Japan. Recently, benefits afforded by phlorotannins in the treatment of various clinical conditions have been reported, but any therapeutic effects of such materials in the treatment of neurodegenerative diseases such as stroke remain unclear. Also, the mechanisms of action of the algal components remain poorly understood. In the present in vivo study, administration of Ecklonia cava polyphenols (ECP) at 10 mg/kg and 50 mg/kg intraperitoneally (i.p.) significantly decreased infarct size and the extent of brain edema in the rat after induction of transient focal ischemia via middle cerebral artery occlusion (MCAO). Further, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay revealed dose-dependent blockage of neuronal apoptosis upon intravenous ECP treatment. Neurobehavioral tests performed over the 6 days after MCAO revealed a reduction in neurological motor performance in control animals, but administration of ECP (50 mg/kg i.p.) prevented this decline. In vitro , a significant neuroprotective effect of ECP was evident when cell viability was assayed after induction of H₂O₂-mediated oxidative stress, upon retinoic acid treatment, in the differentiated neuroblastoma cell line SH-SY5Y. Interestingly, ECP blocked the rise in cytosolic calcium, in a dose-dependent manner, in differentiated SH-SY5Y cells exposed to H₂O₂. Together, the results suggest that ECP exerts neuroprotective effects in the focally ischemic brain by reducing Ca²⁺-mediated neurotoxicity.