We fabricated a fourth generation glucose biosensor using CeO2@CuO core shell nano structure (CeCCS NSs). A simple leave extract of Ocimum tenuiflorum was used to prepare different wt% of 0.2, 04, 0.6, and 0.8 CuO (shell), above 1 wt% of CeO2 (core). The successful formation was confirmed by various characterization techniques like XRD, Uv–Vis, FTIR, SEM and HR-TEM. In the biosensor, 0.4 wt% of CeCCS NSs has shown efficient properties due to its high surface area. The good conductivity and high catalytic activity towards glucose sensing properties were estimated by screen-printed electrode (SPE). The ampherometric studies of CeCCS/SPE modified electrode have been optimized at potential + 0.4 V, showed a sensitivity of 3319.83 μAm M−1 cm−2 within detection limit of 0.019 μM. More significantly, modified electrodes performed excellently against anti-interference and anti-poisoned activity in glucose sample and exhibited promising results for the sustainable improvement for non-enzymatic sensing applications.