In recent years the pharmaceutical industry has strengthened the search for new drugs from natural products. In this context, marine algae have been an important source for the extraction of compounds with diverse biological activity. The seaweed Halimeda opuntia has antioxidant properties associated with the inhibition of lipid peroxidation; however, its possible cytoprotective effect against oxidative stress induced has not been studied. Therefore, the objective of this work is to evaluate the antioxidant and cytoprotective properties of the aqueous seaweed extract Halimeda opuntia in sheep erythrocytes and the H-125 cell line, as well as the relationship of such properties with the chemical composition and polyphenol content totals. The aqueous extract was able to inhibit AAPH-induced hemolysis in sheep erythrocytes with a dose-dependent response at concentrations between 12.5 and 100 mg / mL. The protection to H-125 cells line against H2O2-induced damage was demonstrated, dose-dependent concentrations between 200 and 800 µg / mL. In addition, the extract has reducing power, properties that are associated with the presence in this seaweed of 3 coumarins, and 3 phenolic acids, which justifies the antioxidant activity reported in this work.