This review focuses on macroalgae-derived compounds with neuroprotective activity that may provide lead compounds for the prevention and treatment of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. Coverage is provided from 1999 to 2015. A total of 99 pure compounds have been reported. The main in vitro bioactivities of these compounds include inhibition of beta amyloid protein (Aβ), inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), reduction in oxidative stress, anti-inflammatory activity, inhibition of kinases, enhancement of neurite outgrowth and the reduction in dopaminergic neurotoxicity. The majority of these bioactive compounds are derived from Phaeophyceae (57.6 %), followed by Rhodophyta (28.3 %) and Chlorophyta (14.1 %). This review presents valuable knowledge on macroalgae-derived compounds and their known pathways of neuroprotection to further explore the potential of these compounds in preventing and treating neurodegenerative diseases.