Cinnamaldehyde analogues are a class of chemical substances originated from derivatization of cinnamaldehyde, and are structurally characterized by the presence of cinnamoyl moiety. Due to the presence of highly reactive α,α-unsaturated carbonyl pharmacophore (Michael acceptor) in their structures, these molecules are apt to react with some enzymes and/or receptors as electrophiles, and consequently produce diverse therapeutically relevant pharmacological functions. Naturally occurring molecules, trans-cinnamaldehyde (CA), 2-benzoyloxycinnam-aldehyde (2-BCA), and 2- hydroxycinnamaldehyde (2-HCA) are representatives of this group, and have attracted lots of interest for their bioactivities, especially the anti-cancer and anti-inflammatory properties. Owing to the potential of CA, 2-BCA, and 2-HCA as therapeutic agents, researches on chemical syntheses and modifications have been carried out to gain chemical entities with potent bioactivity and favorable druggability. This review summarizes the progress on phytochemical and pharmacological aspects of natural cinnamaldehyde analogues, illustrate the representative of synthetic molecules with potent bioactivity, and discuss their potential as therapeutic agents.