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The graphical abstract representing the role of Bakuchiol on different immunological parameters. • Bakuchiol isolated from Psoralea corylifolia a folkloric medicinal plant well known for its tremendous medicinal properties. • Anti-inflammatory potential of Bakuchiol was evaluated in in-vitro and in-vivo assays. • Bakuchiol found to be immunosuppressive in various in-vitro and in-vivo assays. • Bakuchiol blocks the phosphorylation of IKKα/β, IκBα and NF-κBp65 thereby exhibiting anti-inflammatory potential. Bakuchiol (BAK) has been reported to have a diverse pharmacological property as an antibiotic, anti-cancer, anti-hypolipidemic, anti-inflammatory and anti-convulsant agent. This study aimed to elucidate the immunomodulation and anti-inflammatory mechanism of bakuchiol using lipopolysaccharide stimulated RAW 264.7 macrophages and various animal models. The present study has shown that BAK significantly suppressed the pro-inflammatory cytokine expression in a dose-dependent manner and its oral administration significantly decreased delayed hypersensitivity responses as compared to control group. The assessment of immunomodulatory activity was carried out by the testing Hemagglutinating antibody (HA) titer, delayed type hypersensitivity (DTH) responses and phagocytic index by carbon clearance test. On the other hand, it showed significant decrease in circulating antibody titer and carbon clearance assay in a concentration-dependent manner. BAK has significantly potentiated the cellular immunity as well as humoral immunity by facilitating the footpad thickness responses in sheep RBCs in sensitized mice by significantly decreasing circulating antibody titer. Molecular studies revealed that BAK inhibited the activation of upstream mediator nuclear factor-κB by suppressing the phosphorylation of IκBα and p65. The responses were statistically significant as compared with the control (* p < 0.05, ** p < 0.01). [ABSTRACT FROM AUTHOR]