Ecklonia maxima, a brown alga grows abundantly on the west coast of South Africa and is used to produce alginate, animal feed, nutritional supplements and fertilizer. The crude extract, solvent fractions and phlorotannins isolated from E. maxima were evaluated for acetylcholinesterase (AChE) inhibitory activity using the microplate technique. The IC50 values for the solvent fractions ranged from 62.61 to 150.8 μg/mL, with the ethyl acetate fraction having the best inhibitory activity against AChE. Repeated column fractionation of the ethyl acetate fraction on Sephadex LH-20 resulted in isolation of three compounds identified as: 1,3,5-trihydroxybenzene (phloroglucinol) (1), together with two of its derivatives dibenzo [1,4] dioxine-2,4,7,9-tetraol (2) and hexahydroxyphenoxydibenzo [1,4] dioxine (eckol) (3). The spectra data of compound 2 is reported for the first time. Structure elucidation of the isolated compounds was carried out using spectroscopic techniques: mass spectrometry (ESI-TOF-MS), 1 H and 13C NMR, DEPT together with 2D experiments (GCOSY, GHSQC and GHMBC). The IC50 values for the compounds ranged from 76.70 to 579.32 μM, with compounds 2 and 3 having the best AChE inhibitory activity. The activity demonstrated by the extracts and the isolated compounds suggests that they could be used as functional food ingredients for the management of neurodegenerative disorders.