Among 36 species of the genus Livistona (family Palmae or Arecaceae), L. carinensis is considered the only species native to Africa. Previous studies showed the richness of Livistona fruits in phenolic compounds. The goal of the current study was to investigate the phytochemical composition and assess the antiviral mechanisms of the L. carinensis leaves’ ethanolic extract cultivated in Egypt for the first time. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) was applied. Moreover, the total crude extract was fractionated using ethyl acetate and n-butanol for phytochemical investigations by various chromatographic and spectroscopic techniques. Besides, the antiviral activity of L. carinensis leaves was assessed using three protocols in vitro using MTT assay compared to acyclovir. UHPLC-QTOF-MS/MS-based analysis resulted in identification of 72 metabolites tentatively. They belonged to diverse phytochemical classes, mainly including flavonoids (29), organic acids (10), and phenolic acids (7). The antiviral activity investigations revealed a direct Adeno virus inactivation mechanism rather than inhibition of virus replication or blocking its attachment to Vero cells. Hence, the plant leaves may be a potential candidate for discovery of novel antiviral drugs owing to the diversity of identified phytochemical classes.