Silicon (Si) is beneficial in mitigating drought stress in plants. Although the effect of Si on plant growth and development has been addressed, there is little knowledge about Si nanoparticles in improving legumes yield when exposed to drought stress. Therefore, the present study was conducted to discover Si on plant growth, biochemical attributes, and fatty acids (FAs) profile of cowpea (Vigna unguiculata [L.] Walp) under drought stress. A split-plot study was carried out in 2020 and 2021 with foliar applications of SiO2 at 50 and 100 mg L-1 in the subplots and irrigation regimes (irrigation after 60, 100, and 140 mm evaporation from Class A pan) in the main plots. The results represented the beneficial function of SiO2 NPS in modulating drought stress. Accordingly, severe drought led to significant declines in biological (33%), seed yield (54%), and relative water content (RWC, 20%), while SiO2 increased these traits by mitigating the drought rate. Compared with normal irrigation and without Si spraying, severe drought results in increases in total soluble sugar (TSS, 95%), malondialdehyde (MDA, 89%), proline (62%), catalase (CAT, 1.4-fold), and superoxide dismutase (SOD, 61%) activities. However, 20, 33, 31, and 12% declines in TSS, MDA, CAT, and SOD were observed with SiO2 at 100 mg L-1 compared with the non-Si application under severe drought. The FA profile showed that drought reduced monounsaturated fatty acids (MUFAs) but increased polyunsaturated fatty acids (PUFAs). According to principal component analysis (PCA), biological yield, seed yield, and RWC showed similar trends under the treatments. Agglomerative hierarchical clustering (AHC) showed that severe drought stress was specified in a distinguished cluster for all traits. The use of silicon dioxide at 50-100 mg L-1 can be effective in alleviating drought stress in cowpea plants, which can be beneficial for agricultural sector to develop the production of this crop in areas with limited water resources.