The present study evaluated ethanolic extracts of two seaweed species brown (sargassum wightii) and red (Gracelaria edulis), collected from Red sea, Egypt with respect to their antimicrobial, antioxidant, and anti-inflammatory activities as well as cytotoxicity. ‘The sargassum wightii extract showed the highest antioxidant activity (IC50 values were 25 and 35 μg/mL, respectively), Meanwhile, (the scavenging % value determined by DPPH method , total phenolic content were (75.49 ± 0.12 and 70.08 ± 0.34 mg Gallic acid equivalent/ gram on dry weight, respectively). Cytotoxicity assay for S. wightii and G. edulis extracts showed strong activity against tested cell lines (Caco-2 and HepG2) cell lines compared to Doxorubicin. Significant differences were also observed in anti-inflammatory activity of ethanol extracts of various investigated seaweeds used. The human red blood cells (HRBC) membrane stabilization method, results showed the high effect of G. edulis than S.wightii as anti- inflammatory in range of concentrations (100-1000) μg/mL compared with the non-steroidal anti-inflammatory drugs (NSAID) as a standard anti-inflammatory drug. The LC MS/MS analysis showed that most biological activities were refer to the phenolic content (Ellagic acid, Naringin, Carvedilol, Bromophenol, Salicyclic acid) of both tested seaweeds. From these results, it could be concluded that the prominent bioactive compounds in tested seaweeds have the potential to treat a wide range of serious diseases. The potential activities of specific bio compounds may be valuable in the pharmaceuticals, cosmeceutical, and functional foods industries.