Plant glutamine synthetase (GS, EC6.3.1.2) catalyzes the synthesis of glutamine from glutamate and ammonium ions and acts as a key enzyme in the nitrogen metabolic pathway in organisms. Nitrogen is an essential element for plant growth and development and plays an important role in crop yield and quality formation. Therefore, GS is crucial in many physiological processes in plants. Currently, nitrogen regulation by GS in plants is well-studied in terms of its effect on plant growth and development. This article reviews the regulatory role of plant GS and its molecular mechanism in mitigating stress injury, such as low or high temperature, salinity, drought and oxidation. The function of plant GS in stress tolerance response is focused. The review aims to provide a reference for the utilization of plant GS in crop stress tolerance breeding.