Malaria is a major health problem in many developing countries. The drugs resistant Plasmodium falciparum causes the most virulent form of malaria in humans and it is described as a public health disaster causing increased morbidity and mortality. Thirteen seaweeds species which belong to four different families (Rhodomelaceae, Cladophoraceae, Ulvaceae, and Caulerpaceae) were collected from Mandapam coastal area and the seaweeds extracts were tested for in vitro antiplasmodial activity against P. falciparum. Among them, Caulerpa toxifolia (IC(50) 5.06 μg·ml(-1)) showed potential antiplasmodial activity than other seaweeds extracts and it can be comparable with the positive control artemether (IC(50) 4.09 μg·ml(-1)). Caulerpa peltata (IC(50) 16.69 μg·ml(-1)) also exhibited good antiplasmodial activity and the IC(50) value is lesser than the positive control chloroquine (IC(50) 19.59 μg·ml(-1)). Statistical analysis reveals that significant in vitro antiplasmodial activity (P<0.05) was observed between the concentrations and time of exposure. The chemical injury to erythrocytes was also carried out and it shows that no morphological changes in erythrocytes by the ethanolic extract of seaweeds extracts after 48 h of incubation. The in vitro antiplasmodial activity might be due to the presence of sugars, proteins, and phenols in the ethanolic extracts of seaweeds. It is concluded from the present study that, the ethanolic extracts of seaweeds of C. toxifolia and C. peltata possesses lead compounds for development of antiplasmodial drugs.