ABSTRACTAlzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple pathological consequences such as oxidative stress, inflammation, apoptosis, cholinergic deficit, amyloid plaques, and tangles formation. Hence, development of drugs with multiple targets will be effective in the treatment of AD. The present study aims at evaluation of the neuroprotective effect of Gelidiella acerosa against amyloid beta 25–35 (Aβ 25–35) induced toxicity in PC12 cells. The antioxidative effect was evaluated by monitoring levels of antioxidant enzymes. Protection against ROS-induced damage was assessed by the measurement of lipid peroxidation, protein carbonyl content (PCC), 2′,7′–dichlorofluorescein diacetate (DCFH-DA) fluorescence, and nitric oxide (NO) production. The cholinesterase (ChE) inhibitory activity was also evaluated. The antiapoptotic activity was verified by caspase-3 activity. The results of antioxidant assays suggest that G. acerosa significantly (P < .05) restores the levels of antioxidant enzymes. Moreover, the seaweed extract was found to prevent the formation of intracellular ROS induced by Aβ 25–35 and thereby protects PC12 cells from macromolecular damage. The study demonstrated that G. acerosa inhibits ChE activity significantly (P < .05) in PC12 cells. The significant decrease (P < .05) in the level of caspase-3 activity indicates that the seaweed has anti-apoptotic activity. Hence, the outcome of this study signifies the neuroprotective effect of G. acerosa targeting multiple pathological consequences of AD.