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The red algae, Acanthophora spicifera, are major species grown in Asia and Pacific areas, especially along the coast of southern Thailand. They have the fast growth rate that leads to an abundant supply; thus, they are currently used for wastewater treatment. Furthermore, an ethanolic extract from A. spicifera has been used as a food supplement because of its perceived antioxidant property. Therefore, this study aims to ascertain and evaluate the antioxidant activity and safety of the ethanolic extract from A. spicifera. Safety tests showed that the extract did not have cytotoxicity and genotoxicity effects at concentrations less than 100 µg/mL. In term of antioxidant activity, the DPPH and ABTS assays showed a Trolox equivalent antioxidant capacity (TEAC) of 5.24±0.44 and 4.03±0.13 mg Trolox/g of the extract, respectively. In conclusion, A. spicifera extract is relatively safe and has a rather high efficacy in scavenging free radicals, which makes it suitable for use as food supplement and cosmetics. However, there are a number of caveats regarding its uses in terms of excessive concentrations and exposure duration to avoid causing cytotoxicity and genotoxicity.