Aegiceras corniculatum (L.) Blanco is known to exhibit anticancer effects against different types of cancer; however, to the best of our knowledge, the anticancer activity and underlying mechanisms of action of A. corniculatum leaf extract on colorectal cancer have not been elucidated. In the present study, colony-forming assay, western blot analysis, flow cytometry, and a xenograft model were used to investigate the effects of an n-butanol extract of A. corniculatum leaves (NACL) on colorectal cancer in vitro and in vivo. The results showed that NACL inhibits the viability and proliferation of colorectal cancer cells in a dose-dependent manner. Besides, NACL also induces cell apoptosis and cell cycle arrest by activating Forkhead box proteins and controlling the cell cycle checkpoint pathways, which are associated with the caspase-dependent mitochondrial apoptotic cascades and Bcl-2 family proteins. More importantly, the tumour sizes in HT-29 xenograft nude mice decreased after treatment with NACL in vivo. These findings indicate that A. corniculatum leaf extracts have potent anticancer activities across different colorectal and other solid tumour cell lines, via regulation of the cell cycle and apoptosis; thus, it has the potential to be developed as an anticancer agent to enhance clinical standards of care for patients with colorectal cancer.