The liver is a crucial organ that regulates the body’s metabolism, detoxification, and immunity, among various other functions. Chronic liver diseases (CLDs) present considerable health concern, especially in the developing countries, leading to around two million deaths each year. Conventional treatment therapies often entail significant side effects, highlighting an urge to introduce safer alternatives. Plant-based bioactive phytochemicals are grabbing interest due to their hepatoprotective properties, providing a natural way to mitigate liver damage caused by various hepatotoxins, drug-induced injuries, and chronic liver disease. Phytochemicals like flavonoids, saponins, alkaloids, polyphenols, and terpenoids directly attenuate reactive oxygen species (ROS) through the nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathway. Moreover, some phytochemicals downregulate nuclear factor-kappa B (NF-κB), hepatic stellate cells (HSCs), and transforming growth factor-beta (TGF-β) as a hepatoprotection mechanism. Furthermore, modulation of mitochondrial and death receptor-mediated apoptotic pathways, autophagy, and AMP-activated protein kinase (AMPK) pathways by phytochemicals can contribute to CLD management. This chapter provides an in-depth review of the natural hepatoprotective mechanisms that may protect and rebuild liver health, paving the way for plant-based treatment options for CLD.