Serevenia buxifolia is an evergreen citrus plant and has attracted considerable attention due to its bioactive components and biological activities. In the present study, the essential oil (EO) from S. buxifolia cultivated in Vietnam was demonstrated to exhibit the in vitro antioxidant, thrombolytic, anti‐hemolysis, anti‐inflammatory, and antidiabetic activities. Briefly, the gas chromatography coupled to mass spectrometry analysis revealed that the leaf EO of S. buxifolia was composed of 33 components, with the main constituents being β‐carypphyllene (32.5%), and elixene (9.8%). The extracted oil possessed a fairly high free radical scavenging activity against 2, 2‐diphenyl‐1‐picrylhydrazyl (DPPH), with an IC50 value of 190.7 μg/mL compared with positive control, α‐tocopherol, IC50 value of 42.6 μg/mL. The EO also exhibited thrombolytic activity: the percentage of inhibition was found to be 70.75% at 100 μL, in comparison with 87.2% for the positive control, streptokinase. For hemolytic activity, the percentage of inhibition of the EO was from 27.4% to 59.6% at concentrations from 10 to 100 μg/mL, respectively. The results of in vitro anti‐inflammatory activity indicated that the EO of S. buxifolia leaves effectively protects the heat‐induced denaturation, with an IC50 value of 40.25 μg/mL. The EO also exhibited antidiabetic potential, with IC50 values of 87.8 and 134.9 μg/mL against α‐amylase and α‐glucosidase, respectively. It is noteworthy that the potent biological activities of the obtained S. buxifolia oil increased in a dose‐dependent manner. The results achieved show that the EO of S. buxifolia leaves can be a potential source for oxidative stress, inflammatory, and diabetic management.