The paper aims to select the appropriate amount of fertilizer and irrigation of Glehnia littoralis in coastal saline alkali land, reduce the loss of nitrogen and improve the efficiency of water and fertilizer utilization and standardize the planting of G. littoralis. The effects of water and fertilizer coupling on plant height, antioxidant enzyme activity index, osmoregulation substances and active components of G. littoralis in rapid growth period were studied, and the best combination of water and fertilizer coupling application was selected and verified by field experiment. The results show that in the whole growth process of G. littoralis, the plant height increased the fastest from the middle of June to early August; water and fertilizer coupling had a significant effect on plant growth of G. littoralis; under the condition of sufficient water, the plant height of G. littoralis could be significantly increased by applying fertilizer. Under the condition of water stress, the activities of SOD, CAT and POD in the leaves of G. littoralis increased with the appropriate application of nitrogen fertilizer, while those in the leaves of G. littoralis decreased with the increase of soil water content at the same fertilization amount; the activities of SOD, CAT and POD were the highest on 40 d (W2F3), 40 d (W2F3), and 60 d (W3F2), which were 38.246, 89.761 and 85.222 U/(g·FW), respectively. Under the same water condition, the contents of soluble sugar, soluble protein and free proline in leaves increased with the increase of fertilizer application amount; under the same fertilization condition, those in leaves decreased with the increase of soil water content; the soluble sugar content of W2F3 (relative soil water content of 60%-70%, and fertilizer amount of 240-360 kg/hm2) treatment group was 26.6% higher than that of W2F1 (relative soil water content of 60%-70%, and fertilizer amount of 120-180 kg/hm2) treatment group, soluble protein content of W2F2 (relative soil water content of 60%-70%, and fertilizer amount of 180-270 kg/hm2) treatment group was 47.11%-90.47% higher than that of W2F1 treatment group, and free proline content of W2F3 treatment group was 11.93%-36.95% higher than that of W2F1 treatment group. Moderate and mild water stress coupled with appropriate nitrogen and potassium nutrition could greatly stimulate the synthesis of coumarins in G. littoralis, in which, the total content of coumarins in W2F2 treatment group was the highest (0.011%). The comprehensive study shows that under mild and moderate water stress condition, the application of N/K fertilizer is beneficial to improving antioxidant enzyme activity and accumulating osmoregulation substances and coumarins, which is very important for plant growth under abiotic stress.