The non-toxic anticancer agents are targeted by researchers in the biomedical field around the world. Natural phytochemicals have been potentially identified in several medicinal plants for cancers therapy. Apoptosis is a programmed cell death of great interest to study mechanism of cancer treatment. This study aimed to investigate the antioxidants activities of the peanut peels extract (PPE) and its possible apoptotic effects on colorectal cancer cell lines (CaCO2). Phytochemicals composition was determined by evaluating the total phenolics, flavonoids, total antioxidant capacities and DPPH scavenging activities. Then, the anticancer activity was evaluated by determining the inhibitory concentrations that kill 50% (IC50) of CaCO2 using MTT assay. The apoptotic pathway of the extract was proved by gene expression analysis using real time polymerase chain reaction (RT-PCR) of Bax, caspase 3 and Bcl-2 genes. The results showed that PPE exhibited potent antioxidant activities and induced apoptosis in human CaCO2 cells by up-regulating Bax and caspase 3 and down-regulating Bcl2 genes. The peanut peel extract could inhibit CaCO2 cellular proliferation due to their phytochemical contents by targeting apoptosis that inhibit colon cancer growth.