This present study aimed to evaluate and investigate the antioxidant, free radical scavenging activity and hepatoprotective activity of the cold macerated water extract of leaves of Rumex napalensis. This study explored the potential pharmacological properties of Rumex napalensis water extract (RN-WE) through a series of in vitro assays. Initially, the extraction process using cold maceration with water yielded a high percentage yield of 9.1%, indicating efficient extraction of bioactive compounds. Phytochemical analysis of RN-WE revealed the presence of phenols, flavonoids, saponins, alkaloids, phytosterols, and anthocyanins, highlighting its diverse chemical composition. Subsequent antioxidant assays demonstrated potent DPPH radical scavenging activity of RN-WE, surpassing the standard antioxidant BHT in certain concentrations, and exhibiting a dose-dependent response. Additionally, the extract exhibited remarkable total antioxidant capacity comparable to or even higher than standard antioxidants BHA and α-Tocopherol, further indicating its strong antioxidant potential. Moreover, RN-WE demonstrated significant hepatoprotective effects against CCl4-induced hepatic injury in HepG2 cells, with higher concentrations showing greater efficacy in improving cell viability. These findings underscored the promising therapeutic potential of RN-WE as a natural antioxidant and hepatoprotective agent, warranting further exploration for its clinical applications in combating oxidative stress-related diseases and liver disorders.