In this study, we aimed to investigate the anti-CRC properties of the alkaloids coclaurine and reticuline through the VDR by assessing the wound-healing process, cell viability, VDR cellular localization, and the gene expression of VDR and its target (i.e., SNAIL1 and SNAIL2) in CRC cells using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9-edited HCT116-VDR/knockout (KO) and wild-type (WT) HCT116 cell lines in comparison with the main VDR ligand, VitD3. Here, VDR is linked to colorectal carcinoma.