Selenium nanoparticles (SeNPs) are gaining attention for their potential therapeutic applications in various diseases, including rheumatoid arthritis, inflammatory bowel disease, asthma, liver disorders, autoimmune disorders, cancer, diabetes, and infectious diseases. Despite their promising properties, challenges such as finding suitable targets and enhancing stability through functionalization techniques remain. This review aims to summarize recent advancements in SeNP functionalization methodologies and their biomedical applications, particularly in anticancer, anti-inflammatory, and anti-infection therapeutics. SeNPs have shown potential in suppressing viral epidemics, such as COVID-19, and their unique characteristics, including high permeability and nontoxicity, make them attractive for targeted drug delivery. The synthesis methods of SeNPs, including biological, physical, and chemical approaches, are discussed, highlighting the importance of surface sealing agents in regulating size, durability, and cellular uptake. SeNPs have demonstrated significant therapeutic efficacy in inflammatory diseases, ulcerative colitis, Crohn's disease, psoriasis, asthma, atherosclerosis, liver injury, diabetes, and cancer. They exhibit anti-inflammatory, antioxidant, and antiproliferative properties, and their ability to modulate signaling pathways and induce apoptosis makes them promising candidates for clinical translation. However, long-term biological consequences and biosafety are areas that require further investigation. Overall, SeNPs show great potential in addressing various health challenges and could be a valuable tool in personalized medicine.Selenium nanoparticles (SeNPs) are gaining attention for their potential therapeutic applications in various diseases, including rheumatoid arthritis, inflammatory bowel disease, asthma, liver disorders, autoimmune disorders, cancer, diabetes, and infectious diseases. Despite their promising properties, challenges such as finding suitable targets and enhancing stability through functionalization techniques remain. This review aims to summarize recent advancements in SeNP functionalization methodologies and their biomedical applications, particularly in anticancer, anti-inflammatory, and anti-infection therapeutics. SeNPs have shown potential in suppressing viral epidemics, such as COVID-19, and their unique characteristics, including high permeability and nontoxicity, make them attractive for targeted drug delivery. The synthesis methods of SeNPs, including biological, physical, and chemical approaches, are discussed, highlighting the importance of surface sealing agents in regulating size, durability, and cellular uptake. SeNPs have demonstrated significant therapeutic efficacy in inflammatory diseases, ulcerative colitis, Crohn's disease, psoriasis, asthma, atherosclerosis, liver injury, diabetes, and cancer. They exhibit anti-inflammatory, antioxidant, and antiproliferative properties, and their ability to modulate signaling pathways and induce apoptosis makes them promising candidates for clinical translation. However, long-term biological consequences and biosafety are areas that require further investigation. Overall, SeNPs show great potential in addressing various health challenges and could be a valuable tool in personalized medicine.