<p>Glutamine is the first amino acid synthesized during nitrogen assimilation and is essential for protein synthesis, amino acid biosynthesis, and various regulatory processes in plants. In rice (<i>Oryza sativa</i>), glutamine not only supports embryogenesis and shoot organogenesis but also plays a pivotal role in modulating stress and defense responses. This review synthesizes findings from over 120 studies conducted across 33 countries, highlighting recent advances in glutamine signaling, sensing, and its role in plant defense mechanisms. In rice, glutamine is a key regulator of protein biosynthesis and nitrogen metabolism, significantly impacting plant growth and stress adaptation under challenging environmental conditions. It initiates long-distance signaling pathways that enhance resistance to biotic stresses, such as pathogen infections, and tolerance to abiotic stresses, including salinity, metal toxicity, water scarcity, and heat stress. Transcriptomic analyses have further elucidated glutamine’s involvement in activating stress-related defense genes and biochemical pathways critical for maintaining plant health. Moreover, glutamine homeostasis and its interaction with the GABA pathway regulate carbon and nitrogen (C/N) metabolism in plant cells, optimizing energy use for gene expression and defense responses. Exogenous glutamine and GABA applications have been shown to mitigate stress effects and enhance pathogen resistance. Additionally, glutamine influences light- and nutrient-dependent synthesis of phytochemicals, contributes to redox balance, and upregulates key defense mechanisms against both biotic and abiotic stressors. Collectively, these findings underscore the multifaceted and central role of glutamine in sustaining rice growth and resilience under adverse conditions.</p>