Nrf2 is a transcription factor that regulates cellular defense against oxidative and metabolic stress, playing a key role in modulating immune responses. This review discusses the role of Nrf2 in immune cell regulation, particularly in inflammatory diseases, and explores the therapeutic potential of Nrf2 activators. Nrf2 activation can reduce oxidative stress and inflammation by modulating redox status and metabolic reprogramming in immune cells. Nrf2 activators, such as sulforaphane, dimethyl fumarate, myricetin, resveratrol, mangiferin, isoastilbin, quercetin, and nitro-fatty acids, have shown promise in preclinical and clinical studies for their anti-inflammatory and immunomodulatory effects. These compounds can reduce the production of pro-inflammatory cytokines, enhance antioxidant defenses, and modulate immune cell function. The review also highlights the importance of Nrf2 in immune cell metabolism and its potential as a therapeutic target for inflammatory diseases. The application of Nrf2 activators in inflammatory diseases is discussed, along with the challenges and opportunities in developing effective therapies. Overall, Nrf2 activation offers a promising approach for modulating immune responses and mitigating the adverse effects of inflammation in various diseases.Nrf2 is a transcription factor that regulates cellular defense against oxidative and metabolic stress, playing a key role in modulating immune responses. This review discusses the role of Nrf2 in immune cell regulation, particularly in inflammatory diseases, and explores the therapeutic potential of Nrf2 activators. Nrf2 activation can reduce oxidative stress and inflammation by modulating redox status and metabolic reprogramming in immune cells. Nrf2 activators, such as sulforaphane, dimethyl fumarate, myricetin, resveratrol, mangiferin, isoastilbin, quercetin, and nitro-fatty acids, have shown promise in preclinical and clinical studies for their anti-inflammatory and immunomodulatory effects. These compounds can reduce the production of pro-inflammatory cytokines, enhance antioxidant defenses, and modulate immune cell function. The review also highlights the importance of Nrf2 in immune cell metabolism and its potential as a therapeutic target for inflammatory diseases. The application of Nrf2 activators in inflammatory diseases is discussed, along with the challenges and opportunities in developing effective therapies. Overall, Nrf2 activation offers a promising approach for modulating immune responses and mitigating the adverse effects of inflammation in various diseases.