Phytochemicals derived from plants have attracted attention as feed additives in aquaculture due to their natural bioactive properties. These compounds have a wide range of benefits such as improving fish growth, increasing feed efficiency, and enhancing immunity. As natural alternatives to synthetic chemicals and antibiotics, phytochemicals contribute to disease resistance, reducing oxidative stress, and promoting gut health in aquatic animals. Betaine, a natural compound with osmotic and metabolic functions, has become a suitable feed additive in aquaculture due to its potential benefits for fish health. The role of betaine in maintaining cellular osmotic balance and enhancing physiological processes such as protein synthesis has made it an effective dietary supplement for enhancing fish growth. Recent studies indicate that this compound not only supports growth performance but also plays a fundamental role in enhancing fish immunity. Betaine enhances the innate defense mechanisms of fish against pathogens by increasing the activity of immune cells, especially macrophages, regulating cytokine production, and reducing inflammation. In addition, betaine’s antioxidant properties reduce oxidative stress and improve immune signaling, helping fish maintain optimal immune function even in stressful environments. This comprehensive review aims to investigate the multifaceted role of betaine in improving fish immunity and antioxidant responses and the mechanisms associated with these roles. © © 2025 Morteza Yousefi et al. Aquaculture Nutrition published by John Wiley & Sons Ltd.