The marine algae, namely, Amphiroa fragilissima, Caulerpa scalpelliformis, Gracilaria edulis, Halimeda gracilis, Sargassum wightii, and Ulva reticulata found in the Mandapam coastal region have been screened for agglutinin activity against human (A, B, AB, and O) erythrocytes and sheep, rabbit, and fish erythrocytes. Carbohydrate (0.98 mg/g) and nitrogen (0.14 mg/g) concentration was higher in Halimeda gracilis. Lipid (0.25 mg/g), protein (0.93 mg/g), and mannitol (0.069 mg/g) content was higher in Sargassum wightii. All 6 seaweed species showed positive agglutinin reactions against rabbit erythrocytes. Halimeda gracilis exhibited high hemagglutinin activity against fish and sheep erythrocytes. Caulerpa scalpelliformis and Ulva reticulata exhibited positive reaction against human A, B, AB, and O erythrocytes. The agglutinating activity of both the species was inhibited by simple sugars. Extracts of Caulerpa scalpelliformis showed cytotoxic activity against Hep 2 cell lines in vitro with a 50% inhibitory concentration (IC50) of 250 µg/mL.