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In the present study, SeNPs were synthesized using Melia azedarach leaf extracts and investigated for growth promotion in wheat under the biotic stress of spot blotch disease. The phytosynthesized SeNPs were characterized using UV-visible spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), and Fourier-transformed infrared spectroscopy (FTIR). The in vitro efficacy of different concentrations of phytosynthesized SeNPs (i.e., 100 μg/mL, 150 μg/mL, 200 μg/mL, 250 μg/mL, and 300 μg/mL) was evaluated using the well diffusion method, which reported that 300 μg/mL showed maximum fungus growth inhibition. For in vivo study, different concentrations (10, 20, 30, and 40 mg/L) of SeNPs were applied exogenously to evaluate the morphological, physiological, and biochemical parameters under control conditions and determine when infection was induced. Among all treatments, 30 mg/L of SeNPs performed well and increased the plant height by 2.34% compared to the control and 30.7% more than fungus-inoculated wheat. Similarly, fresh plant weight and dry weight increased by 17.35% and 13.43% over the control and 20.34% and 52.48% over the fungus-treated wheat, respectively. In leaf surface area and root length, our findings were 50.11% and 10.37% higher than the control and 40% and 71% higher than diseased wheat, respectively. Plant physiological parameters i.e., chlorophyll a, chlorophyll b, and total chlorophyll content, were increased 14, 133, and 16.1 times over the control and 157, 253, and 42 times over the pathogen-inoculated wheat, respectively. Our findings regarding carotenoid content …