Amino acids play a crucial role in activating the NRF2 signaling pathway, which is essential for antioxidant and anti-inflammatory functions. This review discusses the relationship between amino acids and NRF2 activation, highlighting their therapeutic potential in various diseases. NRF2 is a transcription factor that regulates endogenous antioxidant responses and is involved in the regulation of protein-protein interactions, including the thioredoxin-glutathione antioxidant system and unfolded protein responses. KEAP1, a sensor protein, modulates NRF2 activity by sensing redox status and regulating its interaction with NRF2. The activation of the NRF2-KEAP1 pathway can be influenced by amino acids through various mechanisms, including the modulation of KEAP1, activation of the PI3K/AKT signaling pathway, induction of oxidative stress, and modulation of gene expression. Essential amino acids such as histidine, isoleucine, methionine, leucine, lysine, threonine, phenylalanine, valine, and tryptophan have been shown to activate NRF2 and exhibit antioxidant and anti-inflammatory properties. Non-essential amino acids such as serine, arginine, glutamine, glycine, and cysteine also play a role in NRF2 activation. However, excessive NRF2 activation can lead to negative effects, including increased oxidative stress and resistance to chemotherapy. The review emphasizes the importance of understanding the role of amino acids in NRF2 activation for the development of new therapeutic strategies for oxidative stress-related diseases.Amino acids play a crucial role in activating the NRF2 signaling pathway, which is essential for antioxidant and anti-inflammatory functions. This review discusses the relationship between amino acids and NRF2 activation, highlighting their therapeutic potential in various diseases. NRF2 is a transcription factor that regulates endogenous antioxidant responses and is involved in the regulation of protein-protein interactions, including the thioredoxin-glutathione antioxidant system and unfolded protein responses. KEAP1, a sensor protein, modulates NRF2 activity by sensing redox status and regulating its interaction with NRF2. The activation of the NRF2-KEAP1 pathway can be influenced by amino acids through various mechanisms, including the modulation of KEAP1, activation of the PI3K/AKT signaling pathway, induction of oxidative stress, and modulation of gene expression. Essential amino acids such as histidine, isoleucine, methionine, leucine, lysine, threonine, phenylalanine, valine, and tryptophan have been shown to activate NRF2 and exhibit antioxidant and anti-inflammatory properties. Non-essential amino acids such as serine, arginine, glutamine, glycine, and cysteine also play a role in NRF2 activation. However, excessive NRF2 activation can lead to negative effects, including increased oxidative stress and resistance to chemotherapy. The review emphasizes the importance of understanding the role of amino acids in NRF2 activation for the development of new therapeutic strategies for oxidative stress-related diseases.