Acute kidney injury represents a significant threat in cardiac surgery regarding complications and costs. Novel preventive approaches are needed, as the therapeutic modalities are still limited. As experimental studies have demonstrated, glutamine, a conditionally essential amino acid, might have a protective role in this setting. Moreover, the levels of glutamine after the cardiopulmonary bypass are significantly lower. In clinical practice, various trials have investigated the effects of glutamine supplementation on cardiac surgery with encouraging results. However, these studies are heterogeneous regarding the selection criteria, timing, dose, outcomes studied, and way of glutamine administration. This narrative review aims to present the potential role of glutamine in cardiac surgery-associated acute kidney injury prevention, starting from the experimental studies and guidelines to the clinical practice and future directions.