In the present work, a noncovalent and eco-friendly approach was proposed to prepare a carbon-black/β-cyclodextrin (CB/β-CD) nanocomposite. CB/β-CD-nanocomposite-modified screen-printed carbon electrodes were applied for the simultaneous determination of the anticancer drug flutamide (Flut) and the environmental pollutant 4-nitrophenol (4-NP). The electrochemical performance of the proposed sensor relied on the conductivity of CB, the different binding strengths of the guests (Flut and 4-NP) to the host (β-CD), and the different reduction potentials of the nitroaromatic compounds. Fascinatingly, the proposed sensor exhibited an excellent electrochemical performance with high sensitivity, selectivity, and reproducibility. The obtained wide linear ranges were 0.05-158.3 and 0.125-225.8 μM for Flut and 4-NP. The low detection limits of 0.016 and 0.040 μM with the higher sensitivities of 5.476 and 9.168 μA μM-1 cm-2 were achieved for the determination of Flut and 4-NP, respectively. The practical feasibility of the proposed sensor was studied in tap-water and human-serum samples.