As one of the most abundant neuropeptides in the central nervous system, cholecystokinin (CCK) has been suggested to be associated with higher brain functions, including learning and memory. In this review, we examined the potential role of the CCK system in declarative memory. First, we summarized behavioral studies that provide evidence for an important role of CCK in two forms of declarative memory—fear memory and spatial memory. Subsequently, we examined the electrophysiological studies that support the diverse roles of CCK-2 receptor activation in neocortical and hippocampal synaptic plasticity, and discussed the potential mechanisms that may be involved. Last but not least, we discussed whether the reported CCK-mediated synaptic plasticity can explain the strong influence of the CCK signaling system in neocortex and hippocampus dependent declarative memory. The available research supports the role of CCK-mediated synaptic plasticity in neocortex dependent declarative memory acquisition, but further study on the association between CCK-mediated synaptic plasticity and neocortex dependent declarative memory consolidation and retrieval is necessary. Although a direct link between CCK-mediated synaptic plasticity and hippocampus dependent declarative memory is missing, noticeable evidence from morphological, behavioral, and electrophysiological studies encourages further investigation regarding the potential role of CCK-dependent synaptic plasticity in hippocampus dependent declarative memory.