Background: Selenium is an essential trace element which is of fundamental importance to human health. Compared to organic and inorganic selenium, selenium nanoparticles (SeNPs) display unique biological and physicochemical properties. Objectives: In this study, we aimed to optimize the extraction parameters of polysaccharides of Grateloupia filicina (GFPs) and investigate the antioxidant activity of SeNPs stabilized by GFPs. Materials and Methods: GFPs were extracted using hot water. The extraction parameters were optimized by performing an orthogonal experiment. SeNPs were prepared under mild conditions using GFP as the modifier and the stabilizer. A scanning electron microscope (SEM) was used to characterize the prepared GFPs-SeNPs. The antioxidant activities of GFPs, SeNPs, and GFPs-SeNPs were compared by measuring 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, hydroxyl radical scavenging activity, superoxide anion radical scavenging activity, and via reducing power assay. Results: The optimal conditions for the extraction were determined as follows: extraction time 5 h, extraction temperature 90°C, and the ratio of water to raw material 100 mL/g. Under these conditions, the yield of GFPs was 50.34% ±0.27%. GFP-decorated SeNPs with an average diameter of 100 nm were synthesized. GFPs-SeNPs showed a higher antioxidant activity compared to GFPs and SeNPs alone. Conclusion: Hot water extraction was found to be efficient in the process of extraction of polysaccharides of G. filicina. GFPs can significantly enhance the antioxidant activity of SeNPs as modifier and stabilizer. GFPs-SeNPs is an efficient radical scavenger and may be explored as a novel antioxidant agent for use in the fields of foodstuff and medicine.