<p>This investigation explores the fabrication of <i>Sargassum hemiphyllum</i> polysaccharide (Shp) stabilized CeO₂ nanoclusters (Shp-CeO₂ NCs). The synthesized Shp-CeO₂ NCs were characterized using various techniques. HR-TEM analysis revealed that the particles were &lt; 10&#xa0;nm and appeared like clusters. Elemental mapping (EDX) and XPS analysis confirmed the purity of Shp-CeO₂ NCs. In addition, Shp-CeO₂ NCs exhibited potent bactericidal and biofilm inhibitory effects against <i>Staphylococcus aureus</i> and <i>Streptococcus mutans</i> upon treatment with 60&#xa0;µg/mL doses. The CCK-8 assay evidenced the cytotoxic effects of Shp-CeO₂ NCs against MDA-MB-231 cells with an IC₅₀ value of 116.47&#xa0;µg/mL. AO/PI staining exposed the presence of apoptotic bodies and necrotic cells upon treatment with an IC₅₀ concentration of Shp-CeO₂ NCs. PI-stained cells revealed that Shp-CeO₂ NCs can cause nuclear damage and fiery red colored nuclei, indicating the dissipated cell membranes. DAPI staining was also performed to identify the nuclear damage. Meanwhile, the detection of Reactive Oxygen Species (ROS) and mitochondrial superoxide production in MDA-MB-231 cells were also confirmed. Most importantly, this is the first investigation to elucidate the potent multifunctional roles of <i>Sargassum hemiphyllum</i> polysaccharide (Shp) stabilized CeO₂ nanoclusters (Shp-CeO₂ NCs). These nanoclusters not only exhibit unique structure but also offered a promising therapeutic strategy in biomaterial research. Therefore, it can be concluded that Shp-CeO₂ NCs can act as a multifunctional hybrid material for various biological and environmental applications.</p> Graphical Abstract <p></p>