Objective: To isolate and identify the polyphenolic constituents of Dypsis lutescens, and evaluate the hepatoprotective activity of the ethanolic extract of Dypsis lutescens leaves. Methods: Hepatoprotective, antioxidant and anti-inflammatory effects of two doses of Dypsis lutescens ethanolic leaf extract were investigated in five groups of six rats each administered with the ethanolic extract of Dypsis lutescens leaves. Liver function parameters were assessed, histopathological study was carried out, the anti-inflammatory mediators and the antioxidant potential in the liver tissues were evaluated. In addition, the total ethanolic extract of Dypsis lutescens leaves was subjected to different chromatographic separation techniques to yield ten phenolic compounds. The isolated compounds structures were spectroscopically elucidated. Results: Hepatoprotective activity of Dypsis lutescens ethanolic extract was estimated for the first time and showed significant activity against histopathological changes induced by D-galactosamine in liver. The extract improved the liver functions. Compared to the D-galactosamine group, the architecture of the liver in the treated groups was improved in the histopathological examination. These results proved the hepatoprotective activity of Dypsis lutescens and its ability in attenuating liver oxidative damage and inflammation. Phytochemical investigations of the total extract afforded ten compounds from the genus Dypsis. Conclusions: The alcoholic extract of Dypsis lutescens exerted potential hepatoprotective action, maintaining liver health and functions.