The anticancer activity of silver nanoparticles (AgNPs) is well known to be synthesized using green-synthesized methods, although its mechanism of action is not understood fully. Moringa oleifera leaves were used as reducing and stabilizing agents to synthesize AgNPs. Green-synthesized AgNPs were characterized using ultraviolet-visible spectroscopy, dynamic light scattering, transmission electronic microscopy, scanning electronic microscopy, Fourier transform infrared, and energy-dispersive X-ray spectroscopy analyses. The synthesized nanoparticles were then characterized by their anticancer properties by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The real-time polymerase chain reaction was used to check the expression levels of the four genes (β-catenin, adenomatous polyposis coli (APC), and lipoprotein receptor-related proteins 5 and 6 (LRP5/6)). The synthesized nanoparticles were 25 nm on average and spherical in shape and aggregated form. Noteworthy cytotoxicity is how green-synthesized M. oleifera–AgNPs were observed in comparison with the M. oleifera leaf extract against a cancerous cell line. The M. oleifera–AgNPs decreased the expression of CTNNB1 and LRP6 genes, while the LRP5 gene expression increased in both cell lines. With treatment, the APC gene expression decreased in SW480 but increased in HTC116. Our results imply that AgNPs synthesized by M. oleifera extract could be an ideal strategy to combat colon cancer.