This review explores the role of amino acids in activating the NRF2 (nuclear factor erythroid 2-related factor 2) signaling pathway, which plays a crucial role in antioxidant and anti-inflammatory responses. Amino acids, being essential components of proteins, exhibit a wide range of biological activities and are significant in medicinal applications. The review highlights how amino acids can activate the NRF2-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway, leading to therapeutic effects in various diseases. It discusses the mechanisms by which amino acids activate NRF2, including direct interaction with KEAP1, activation of the PI3K/AKT signaling pathway, induction of oxidative stress, and modulation of gene expression. The review also delves into the specific roles of essential and non-essential amino acids in NRF2 activation, such as histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, taurine, serine, arginine, glutamine, glycine, and cysteine. Each amino acid's biosynthesis pathway and its impact on NRF2 activation are detailed, along with its potential therapeutic applications. However, the review also notes potential negative effects of amino acid-mediated NRF2 activation, such as metabolic vulnerabilities in cancers and the production of reactive oxygen species (ROS). The conclusion emphasizes the need for further research to understand the complex interactions between amino acids and NRF2, particularly in clinical settings, to develop better therapeutic approaches for oxidative stress and inflammation-related diseases.This review explores the role of amino acids in activating the NRF2 (nuclear factor erythroid 2-related factor 2) signaling pathway, which plays a crucial role in antioxidant and anti-inflammatory responses. Amino acids, being essential components of proteins, exhibit a wide range of biological activities and are significant in medicinal applications. The review highlights how amino acids can activate the NRF2-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway, leading to therapeutic effects in various diseases. It discusses the mechanisms by which amino acids activate NRF2, including direct interaction with KEAP1, activation of the PI3K/AKT signaling pathway, induction of oxidative stress, and modulation of gene expression. The review also delves into the specific roles of essential and non-essential amino acids in NRF2 activation, such as histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, taurine, serine, arginine, glutamine, glycine, and cysteine. Each amino acid's biosynthesis pathway and its impact on NRF2 activation are detailed, along with its potential therapeutic applications. However, the review also notes potential negative effects of amino acid-mediated NRF2 activation, such as metabolic vulnerabilities in cancers and the production of reactive oxygen species (ROS). The conclusion emphasizes the need for further research to understand the complex interactions between amino acids and NRF2, particularly in clinical settings, to develop better therapeutic approaches for oxidative stress and inflammation-related diseases.