Colon carcinoma poses a significant health challenge globally, particularly in developed nations where sedentary lifestyles, poor dietary choices, and genetic factors play a crucial role in its prevalence. Chemotherapy, the primary treatment method, carries severe side effects that can jeopardize patients' lives. Herbal extracts such as Ocimum Basillicum extract have shown effectiveness against cancer cells. Additionally, nanoparticles can significantly enhance drug delivery efficacy in these scenarios. This article aims to investigate the impact of copper nanoparticles coated with Ocimum Bassilicum at chemoradiotherapy of Colon Carcinoma to hopefully create new treatment options with fewer side effects for patients. CuO bio-NPs were produced by the addition of 15 mL of extract dropwise to 80 mL of a 5 mM Cu (OAc)2 aqueous solution, which was then refluxed for 2 h at 100 °C. The mixture gradually became darker brown in color as a result of the heating procedure. The production of CuO NPs and the hydrogen-donating activity of antioxidant phenols within the plant are signaled by surface plasmon resonance excitation, which is the cause of this. In the cell culture, LS174t colon cancer cells were treated with OB extract, CuNPs, and OB-coated CuNPs with and without different radiation levels in order to assess cell viability, through the MTT assay, and the pro-apoptotic BAX and anti-apoptotic BCL2 expressions, through qPCR assay. The results demonstrate a decrease in cell viability and the expression of BCL2 and an increase in the expression of BAX especially when treated with OB-coated CuNPs and even furthermore when paired with radiation therapy. After doing the clinical trial studies, the recent nanoparticles can be used for the treatment of Colorectal carcinoma. •Effect of Ocimum bassilicum extract, Cu NPs, and Ocimum bassilicum -coated CuNPs on LS174t colon cancer cells.•Cytotoxic effects of Ocimum bassilicum -coated CuNPs against LS174t cells.•Intensifier effects of radiotherapy at these survival cells.