[Objective] To investigate the effects of nitrogen fertilizer synergists on wheat growth, yield, and nitrogen use efficiency.[Methods] Five treatments were set up: control（ CK）, U（T1）, U+NBPT（T2）, U+DMPP（T3） and U+NBPT+DMPP（T4）. The fertilizer was applied at the jointing stage through integrated water and fertilizer management. The effects of each treatment on the growth, yield, nitrogen use efficiency, and physiological characteristics of winter wheat were compared. [Results] Compared with T1, treatments T2 to T4 all improved the plant height, dry matter accumulation, and yield. In particular, T4 significantly increased dry matter and yield by 32.35% and 17.19%, respectively. Treatments T2 to T4 significantly improved wheat water and nitrogen use efficiency, as well as the soil nitrogen supply capacity. Under T4, nitrogen uptake efficiency, partial factor productivity, agronomic efficiency, nitrogen contribution rate, and water use efficiency increased by 18.96%, 17.19%, 89.36%, 61.57% and 17.59%, respectively. At the booting stage, the contents of soil NH₄⁺-N, NO₃^--N, and the apparent nitrification rate of NH₄⁺-N were significantly reduced by 6.04%, 18.74% and 5.03%, respectively, compared with T1. Additionally, the activities of soil urease, nitrate reductase, nitrite reductase, and hydroxylamine reductase were significantly reduced by 30.37%, 20.04%, 14.54% and 7.04%, respectively, compared with T1. The application of inhibitors with urea increased the chlorophyll content and antioxidant enzyme activity, reduced malondialdehyde content and superoxide radical production rate, delayed leaf senescence, enhanced nitrogen uptake in the later growth stage, and improved nitrogen use efficiency. [Conclusion] The combined application of NBPT and DMPP with urea promotes wheat growth, optimizes soil nitrogen-metabolizing enzyme activities and leaf physiological characteristics, enhances photosynthetic capacity, delays leaf senescence, and ultimately improves wheat yield and both water and nitrogen use efficiency. It is the optimal strategy for applying inhibitors in integrated water and fertilizer management. The results of this study can provide a basis for the efficient application of nitrogen fertilizer in wheat.