Tong-Xuan TeeLi Ting KeeTsun-Thai ChaiHok Chai YamHasan Mahmud Reza0000-0003-2259-1617Fai-Chu WongJia Xian LawSheri-Ann Tan2024-12-262024-12-262024-12-0710.1007/s43450-024-00609-5https://dspace-cris.utar.edu.my/handle/123456789/8248Excessive reactive oxygen species are harmful to human health due to the spontaneous oxidation of intracellular biomolecules such as deoxyribonucleic acid and proteins. To maintain a homeostatic level of reactive oxygen species, Kelch-like ECH-associated protein–nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) pathway acts as the primary protective response. Nrf2 is a vital transcriptional factor that induces the expression of various oxidative response genes. Nrf2 binds to the antioxidant response element-containing promoters of cytoprotective and antioxidative genes leading to the production of a series of enzymes that detoxify drugs and eliminate pro-oxidants to retain an intracellular redox homeostasis. Nrf2 is also involved in critical signaling pathway associated with liver regeneration. Keap1, on the other hand, is the primary inhibitor of Nrf2. Given that the dysregulation of Keap1-Nrf2 pathway is linked to several non-communicable diseases including liver ailments; thus, activating Nrf2 through the inhibition of Keap1 is crucial for liver health. This review comprehensively examines natural Nrf2 activators derived from plants, including secondary metabolites and peptides that impart antioxidative and regenerative properties to the liver, with a primary emphasis on studies employing in vivo model systems. © The Author(s) under exclusive licence to Sociedade Brasileira de Farmacognosia 2024.enHepatoprotectiveHomeostasisNrf2 activatorPlant compoundsPlant extractsPlant peptidesantioxidantDNAnuclear proteinplant extractreactive oxygen metabolitetranscription factor Nrf2antioxidant responsive elementcell protectioncontrolled studygene expressionhomeostasishumanliverliver regenerationnonhumanoxidationpharmacologypromoter regionratreviewsignal transductiontext::review