Medicinal plants have been used for centuries to fight against all types of diseases, essentially certain types of cancer. In this study, we investigate the potential of Moricandia arvensis chloroform root extract (ChlR) as anticancer agent by evaluating its effect on viable cell number, oxidation, the sensitivity of cancer cells to apoptosis and melanin biosynthesis. ChlR extract decreased the proliferation of Caco-2 and BE cell lines by 99.60 and 95.21%, respectively. Furthermore, the extract exhibited significant inhibitory activity (99.43%) against calpain after 2 h of incubation with Caco-2 cells, suggesting its possible use as an anticancer agent. ChlR also enhanced significant antioxidant activity (IP = 100%) after 2 h of incubation with the two colorectal cancer cell lines and a significant inhibition of melanin synthesis. Targeting calpain using ChlR extract could be an interesting way to prevent and/or treat colorectal cancers; in addition, this extract might be used as a skin whitening agent.