The marine red algae (Gelidiella acerosa and Sargassum wightii) possessing excellent antioxidant and anticholinesterase activity were subjected to toxicity evaluation for a deeper understanding of other bioprotective properties of seaweeds. Cytotoxic evaluation was done by trypan blue exclusion, and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays using human PBMC (peripheral blood mononuclear cells) and RBC (red blood cells) lysis assay using human erythrocytes. Mutagenicity of the seaweeds was analyzed by Ames salmonella mutagenicity test with the histidine dependent mutant strains TA 98, TA100 and TA 1538. Genotoxic activity was verified in PBMC by comet assay. The results suggest that benzene extract of G. acerosa (BEGA) and dichloromethane extract of S. wightii (DMESW) did not show cytotoxic effect both in PBMC and erythrocytes. Evaluation of mutagenic activity suggests that the seaweeds did not cause any mutagenic effects both in the absence and the presence of S9 microsomal fraction in all the three Salmonella mutant strains. Results of genotoxic study showed that PBMC treated with seaweed extracts (1 mg/mL) exhibit less or no damage to cells, thus proving the non-genotoxic effect of the extract. Since these in vitro non-clinical studies clearly demonstrate the non-toxic nature of the seaweeds, they could be exploited for further characterization, which would result in development of novel and safe therapeutic entities.