Japanese quince leaf phenol-rich extract (PRE) represents a good source of phenolic compounds, among which chlorogenic acid and naringenin hexoside are the main constituents. The aim of this research was to evaluate the chemopreventive activity of PRE in human colon cancer (SW-480 and HT-29) and human normal colon cell line (CCD 841 CoN). All cell lines were exposed to different concentrations of the extract (150-500 κg/mL for SW-480 and CCD 841 CoN; and 250-750 κg/mL for HT-29) to investigate migration and invasion, as well as the activity and secretion of metalloproteinases (MMP-2 and MMP-9) involved in these mechanisms. Moreover, the influence of PRE on the activity of ERK and AKT pathways, which are strongly involved in colon cancer development (CRC), were measured. Our results demonstrated that PRE significantly inhibited migration and invasion in SW-480, HT-29 and CCD 841 CoN cells through MMP-2 and MMP-9-dependent mechanisms. We also proved that PRE can effectively downregulate both the activity and protein expression of MMP-2 and MMP-9 in these cell lines. The exception was the higher concentration of PRE, which up-regulated the protein expression of MMP-9 in SW-480. Additionally, we showed that significant inhibition of p-ERK/p-AKT expression in SW-480 after treatment with PRE is involved in chemopreventive effects of this extract. In case of exposure of HT-29 cells to PRE, we observed a significant upregulation of p-ERK protein expression, and suppression of p-AKT mechanism. This research of Japanese quince phenol leaf extract suggests its application in colon cancer prevention and treatment due to its ability to inhibit migration and invasion in MMP-9 and MMP-2-dependent mechanisms via most likely the modulation of ERK and AKT signaling pathways in colon cancer cells. Overall, our results provide an experimental foundation for further research on its potential activities and effects in vivo.