Diarylpentanoid analogues of curcumin are known for their various pharmacological activities which include the inhibition of inflammatory mediators and are good candidates as immunomodulators that could be useful in the treatment of inflammation. In the work described here, seventeen diarylpentanoid curcumin analogues were assessed for their inhibitory effects on the reactive oxygen species (ROS) production, chemotaxis and phagocytosis of human neutrophils. ROS production was evaluated using luminol and lucigenin-based chemiluminesence assay, while inhibition of isolated polymorphonuclear neutrophils chemotaxis and phagocytosis abilities were investigated using the Boyden chamber technique and the Phagotest kit, respectively. Two of the analogues, compounds 1e and 2e, which contain the 2-methyl-4(N-ethyl-N-ethylacetonitrile)aniline functional group, were active in all the assays performed. Moreover, analogues containing heteroatoms (1a, 1e, 2c, 2d, 2e, 3a and 3c) were active in suppressing the neutrophil phagocytic activity. The information obtained gave new insight into curcumin analogues with the potential to be developed as new immunomodulators.