An efficient macroporous resin purification process was designed to obtain food-grade phlorotannin-rich extracts from the seaweeds Durvillaea incurvata and Lessonia spicata. Phlorotannins were profiled to relate structures with the α-glucosidase inhibitory activity of the extracts. Liquid chromatography-mass spectrometry was applied for tentative identification. The best phlorotannin purification performance was achieved with HP-20 resin and elution with 80% v/v ethanol. This is the first study that demonstrates the effectivity of HP-20 resin for removing potentially toxic elements (As, Cd) from seaweed extracts. Fucols/phlorethols/fucophlorethols isomers up to 4 phloroglucinol units (PGU) were the most representative phlorotannins. High molecular weight species (11-21 PGU), although in low abundances, were detected in D. incurvata for the first time. Eckols, carmalols, fuhalols, phenolic acids, and flavonoids were also detected. Some extracts' potent α-glucosidase inhibitory activities were related to their high phlorotannin abundances, the presence of phlorotannins of a high degree of polymerization, and the phlorotannins class.