A series of thirty three 2,6-bisbenzylidenecyclohexanone and pyrazoline derivatives were synthesized and evaluated for inhibitory activities on IFN-c/LPS-activated RAW 264.7 cells and DPPH radical scavenging activity. Compounds 8, 9, and 11a demonstrated significant NO inhibitory activity as compared to L-NAME and curcumin with IC50 values of 6.68 ± 0.16, 6.09 ± 0.46, and 6.84 ± 0.12 lM, respectively. Apparently the suppression upon NO secretion was not due to cell death since the active compounds did not reduce the cell viability in close proximity to the IC50 of NO inhibition. Overall, incorporation of pyrazoline ring as part of the linker chain improved cell viability compared to the 2,6-bisbenzylidenecyclohexanone derivatives. Meanwhile, compound 11 (IC50 = 13.27 ± 1.78 lM) bearing ortho hydroxyls on the aromatic rings recorded the highest radical scavenging activity as compared with quercetin (IC50 = 21.46 ± 0.85 lM).