Cardiovascular diseases are one of the leading cause of mortality and morbidity worldwide. Although many efforts have been made in the drug discovery and development process through decades, the number of approved drugs has been declining. In the recent years, soluble epoxide hydrolase (sEH) has been considered as promising target for drug development since inhibiting sEH function would prevent the formation of arterial thrombosis. Paederia foetida L. is a folk medicine distributed commonly in Vietnam which is well known for its uses in the treatment of various diseases. This study conducted in silico assessment of 21 isolated compounds from leaves of Paederia foetida L. against sEH enzyme for potential inhibition activity. Obtained results demonstrated that compound 4 and 9 could be potent, safe and novel inhibitors based on docking conformation and druglikeness properties.