We studied the effects of exogenous spermidine (Spd) on plant growth and nitrogen metabolism in two cultivars of tomato (Solanum lycopersicum) that have differential sensitivity to mixed salinity-alkalinity stress: ‘Jinpeng Chaoguan’ (salt-tolerant) and ‘Zhongza No. 9’ (salt-sensitive). Seedling growth of both tomato cultivars was inhibited by salinity-alkalinity stress, but Spd treatment alleviated the growth reduction to some extent, especially in ‘Zhongza No. 9’. Exogenous Spd may help reduce stress-induced increases in free amino acids, ammonium (NH4+) contents, and NADH-dependent glutamate dehydrogenase (NADH-GDH) activities; depress stress-induced decreases in soluble protein and nitrate content; and depress nitrate reductase, nitrite reductase, glutamine synthetase (GS), NADH-dependent glutamate synthase (NADH-GOGAT), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) activities, especially for ‘Zhongza No. 9’. Based on our results, we suggest that exogenous Spd promotes the assimilation of excess toxic NH4+ by coordinating and strengthening the synergistic action of NADH-GDH, GS/NADH-GOGAT, and transamination pathways, all during saline-alkaline stress. Subsequently, NH4+ and its related enzymes (GDH, GS, GOGAT, GOT, and GPT), in vivo, are maintained in a proper and balanced state to enable mitigation of stress-resulted damages. These results suggest that exogenous Spd treatment can relieve nitrogen metabolic disturbances caused by salinity-alkalinity stress and eventually promote plant growth.