Selenium (Se), an essential micro compound for plants, has been playing a pivotal role in triggering many physiological and biochemical activities, and helps the plant deal with various biotic and abiotic stresses in agroecosystems. Recent advancements in nanotechnology have led to the emergence of nano-selenium (nano-Se) as a potential alternative to bulk selenium (bulk-Se) due to its unique physicochemical properties conferred due to its nanostructure. Bulk-Se, traditionally applied as fertilizers or supplements, demonstrates bioactivity by enhancing plant growth, stress tolerance, and defense mechanisms. However, it faces limitations in bioavailability and potential toxicity at higher concentrations. Nano-Se, with its smaller size, higher surface area, and enhanced reactivity, shows improved uptake, translocation, and utilization within plant systems, allowing for more efficient stress mitigation at lower dosages. Moreover, nano-Se induces antioxidant and antimicrobial activities, modulates key defense-related enzymes, and enhances the expression of stress-responsive genes, thereby offering superior protection against biotic stressors compared to its bulk counterpart. This chapter highlights the comparative advantages of nano-Se over bulk-Se, emphasizing the potential of nano-selenium as a sustainable and eco-friendly solution for improving plant resilience against biotic and abiotic stresses induced by pathogens, pests, and environmental factors in agroecosystems. Future research is warranted to elucidate further the long-term effects, ecological interactions, and safety of nano-Se applications in agriculture.