Seaweed polysaccharides demonstrate various properties like antiviral, antibacterial, and anti-cancer activity. In this study, low molecular polysaccharides (6–8 kDa) extracted from G. corticata, G. filicina, H. musciformis, L. obtuse, L. papilosa, C. fragile, D. dichotoma, and P. boergesenni were screened for cytotoxicity against HeLa and MCF cell lines. The proximate compositions of polysaccharides like total sugar, reducing sugar, protein and sulfate content varied depending on the species. Polysaccharides of five red and two brown seaweeds were optically positive exhibiting D-form rotations. In contrast, green C. fragile shows L-form with negative rotation, suggesting that it constitutes arabinogalactans over other seven polysaccharides that constitute galactan. The extracted polysaccharides showed cell survivability range of 24–98.6% against HeLa and 4.7–58% against MCF cell lines, and the IC50 value of Codium fragile was lower than the rest of the seaweeds screened. But the >14 kDa fraction of Codium fragile polysaccharide showed pronounced cytotoxic effect against the HeLa cell line, higher antioxidant activities, and was characterized by FTIR as sulfated arabnogalactans. Among eight seaweed polysaccharides, Codium fragile constituting optically negative L-form arabinogalactans have a promising potential to develop into a cancer drug.