Passiflora foetida L. (Passifloraceae), a perennial climber in general, is used for treating many ailments in conventional medicine. In this study, the anti-inflammatory effect of methanolic extracts of P. foetida L. (PFME) and the involvement of nuclear factor-κB (NF-κB) signalling in the regulation of inflammation were investigated. PFME prevented the production of prostaglandin E2 (PGE2) and the expression of inducible cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced macrophage cells. Additionally, PFME reduced the release of pro-inflammatory cytokines. Moreover, in LPS-induced RAW264.7 cells, the phosphorylation of MAPKs (ERK1/2, p38 and JNK) was suppressed by PFME. Furthermore, PFME inhibited the NF-κB activation induced by LPS, which was associated with nuclear p65 levels with the abrogation of IκBα degradation and subsequent decreases. These results indicated that the PFME inhibited the LPS-induced inflammatory and oxidative responses. Therefore, we propose that the PFME may be therapeutic for treating inflammatory diseases.