Opilia celtidifolia is a long-used herb with intriguing biological activity that has been employed in many different medicinal applications. This research aims to evaluate the hepatoprotective and antioxidant properties of the aqueous and ethanolic extracts of Opilia celtidifolia in vitro. Using the DPPH and ABTS tests, the extracts' antioxidant properties were evaluated. The hepatoprotective properties were assessed in HepG2 cell lines subjected to hydrogen peroxide (H2O2)-induced oxidative stress. The hepatoprotective effects were assessed using cell viability, lipid peroxidation, and the activity of the enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The ethanolic extract demonstrated exceptional antioxidant qualities in each test and performed better than the aqueous extract in scavenging free radicals. In the hepatoprotective test, pre-treating HepG2 cells exposed to H2O2 led to a significant increase in cell survival and a reduction in lipid peroxidation. Additionally, both extracts were able to effectively reduce the elevated levels of AST and ALT, with the ethanolic extract exhibiting a somewhat higher protective effect. The findings show that Opilia celtidifolia's ethanolic extract has potent antioxidant and hepatoprotective properties.These results underscore the plant's historic usage in liver-related ailments and its potential as a natural antioxidant and hepatoprotective medication source.