Hepatitis E virus (HEV), a non-enveloped and globular protein, is the primary cause of acute hepatitis. The structural capsid protein encoded by HEV is the open-reading frame 2 gene. However, there are presently no efficient and targeted therapies for HEV infections. This research aims to screen out the effective bioactive compounds from Paederia foetida, which may be novel potential inhibitors of Hepatitis E. Despite various research in recent decades, the molecular picture of the interaction between the Hepatitis E virus and iridoid glycosides from Paederia foetida remains vague. We performed in silico ADMET predictions of the phytochemicals of Paederia foetida, and the findings revealed a reasonably good ADMET profile for the twenty chosen phytochemicals. Herein, the twenty phytochemicals were submitted to an analysis of molecular docking studies with the HEV protein and the analysis suggested that asperuloside, ellagic acid, friedlin, lupeol and paederoside as the most potential HEV inhibitors among the selected phytochemicals. Subsequently, the stability of these phytochemical complexes was studied by using molecular dynamic (MD) simulation of 100 ns. Based on our computational study, lupeol and paederoside phytochemicals obtained from the paederia foetida plant may be used as potential drug candidates for the inhibition of hepatitis E.