<p>Hyperglycemia is a persistent metabolic disease triggered by insufficient insulin synthesis by the pancreas. Phytoconstituents loaded nanoparticles offer better therapeutic profiles compared to chemical-based nanoparticles, but their effectiveness is challenging due to their solubility patterns, absorption kinetics, and lipid barriers. Selenium is a micro mineral necessary for human health that is becoming indispensable for the immune system and thyroid-related hormone metabolism. Selenium plays a crucial role in hyperglycemia due to its role in insulin production, secretion, and inflammation. Its antioxidant bioactivities may increase glutathione peroxidase-1 expression and reduce oxidative stress in islet β-cells. However, selenium management is crucial due to its excessive exposure may increase the risk of hyperglycemia by boosting the synthesis of Sepp1 in the liver, which is known to cause insulin resistance. By minimizing its toxicological profile, increasing its biological compatibility as well as its efficacy, and decreasing its particle size, nanotechnology has increased the potency of selenium. The green process for synthesizing selenium nanoparticles offers an environmentally sustainable alternative to traditional techniques, enhancing the benefits of nanoparticle fabrication. This article delved into the breakthroughs in the synthesis of phyto-selenium nanoparticles (PSeNPs), concerning a spotlight on addressing the complex therapeutic mechanism of action for the treatment of hyperglycemia and stewardship of its accompanying consequences.</p> Graphical Abstract <p></p>