The exaggerated activation of Polymorphonuclear neutrophils (PMNs) can lead to a harmful cycle of persistent inflammation. This study aims to investigate the in vitro and in silico immunomodulatory effects of Laurus nobilis essential oil (LEO) and its main compound, eucalyptol, on PMNs functions involved in inflammatory processes. The immunomodulation effects of LEO and eucalyptol have been studied on both fMLP-PMNs-stimulated degranulation and oxidative burst, in addition to their antioxidant, anti-hemolytic and antiplatelet aggregation activities. We also performed an in silico analysis for LEO and eucalyptol to evaluate their potential inhibitory pathways. Firstly, we showed that LEO and eucalyptol have immunomodulatory activities on PMNs functions. Thus, LEO and eucalyptol inhibit, in a dose-dependent manner, fMLP-induced degranulation of PMNs with maximal percentages of inhibition of 50.44 % and 74.69 %, respectively, and in the same way, reduce oxidative burst with maximal percentages of inhibition of 61.07 % and 51.29 %, respectively (p < 0.001). Secondly, in silico docking of LEO studies showed that its selected major compounds (eucalyptol, α-terpinyl acetate, and β-phellandrene) have an energy change ranging between – 4.2 and – 7.4 kcal/mol on NADPH oxidase, its subunits, and PKC. In addition, LEO and eucalyptol were found to possess significant antioxidant activity with various IC₅₀ and protective capabilities against H₂O₂-induced hemolysis in erythrocytes (p < 0.001), and also inhibited collagen-induced platelet aggregation. The collective findings of this research shed light on the immunomodulatory effects on PMNs functions by LEO and eucalyptol that provide new insights for studying the mechanism pathways of Laurus nobilis L., particularly in the modulation of innate immunity and inflammatory responses