| Summary: | This is the first study to examine the effects of in vitro digestion on biological activities of <i>Sargassum</i> spp., a broadly known brown seaweed for therapeutic potential. Three fractions (F1–F3) were obtained from hexane extract by column chromatography. Under in vitro simulated digestion, the anti-α-amylase capacity of F1 in oral and intestinal phases increases, while it significantly decreases in the gastric phase. The α-amylase inhibition of F2 promotes throughout all digestive stages while the activity of F3 significantly reduces. The cytotoxic activity of F1 against U266 cell-line accelerates over the oral, gastric, and intestinal stages. The fractions F2 and F3 exhibited the declined cytotoxic potentialities in oral and gastric phases, but they were strengthened under intestinal condition. Palmitic acid and fucosterol may play an active role in antidiabetic and cytotoxic activity against multiple myeloma U266 cell line of <i>Sargassum</i> spp. However, the involvement of other phytochemicals in the seaweed should be further investigated.
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