Liver diseases constitute a major global health burden, collectively affecting hundreds of millions of individuals and contributing significantly to morbidity and mortality worldwide. Current therapeutic options, including antiviral agents for viral hepatitis and liver transplantation for end-stage disease, remain constrained by high cost, adverse effects, limited availability, and the absence of universally effective pharmacological agents for conditions such as non-alcoholic steatohepatitis (NASH) and drug-induced liver injury (DILI). Against this backdrop, medicinal plants have emerged as promising and historically substantiated sources of hepatoprotective compounds. This review critically examines the role of medicinal plants in hepatoprotective drug development, with particular emphasis on the biochemical mechanisms underlying their therapeutic actions. Key mechanisms explored include antioxidant reinforcement of the glutathione system, suppression of pro-inflammatory cytokines, modulation of hepatic detoxification enzymes such as cytochrome P450 isoforms, and prevention of fibrogenic activation of hepatic stellate cells. Bioactive constituents including flavonoids, polyphenols, alkaloids, and terpenoids are discussed in the context of their pharmacological profiles and mechanistic relevance. The review further evaluates preclinical evidence from in vitro and in vivo studies, highlights challenges in clinical translation including pharmacokinetic variability and lack of standardized extract formulations, and addresses emerging strategies in novel drug delivery systems. Regulatory and commercialization hurdles are examined critically. The manuscript concludes by delineating future research priorities aimed at bridging the gap between experimental findings and clinical hepatoprotective therapies derived from plant-based sources.