Snake fruit ( Salacca edulis Reinw.) is a tropical fruit produced in Indonesia. Snake fruit peel is normally discarded as waste. In the present study, it was revealed that snake fruit peel has high bioactivities on stimulation of the immune system. Snake fruit peel extract (SFPE) was prepared by extracting snake fruit peel powder in water for 15 h at 4 °C. SFPE enhanced phagocytotic activity of murine macrophage-like J774.1 cells. Production of cytokine such as tumour necrosis factor (TNF)-α and interleukin (IL)-6 was also stimulated by SFPE. The gene expression levels for these cytokines were elevated. Immunoblot analysis revealed that SFPE enhanced not only nuclear factor (NF)-κB but also mitogen-activated protein kinases signalling cascades such as JNK and p38 in macrophage. Overall findings suggested that SFPE has a potential beneficial effect to promote our body health through the stimulation of macrophage.