The screen-printed technique is widely used as an efficient tool for electrochemical analysis in environment, clinical and agri-food areas. Significantly, it has the ability to transfer electrochemical laboratory experiments into the field. In the present work, we report a highly sensitive, simple, low-cost protocol for determination of amlodipine (AML) using bare/unmodified and DNA-modified screen-printed electrodes (SPEs). The immobilization of DNA molecules onto SPE offers promising robust and chemically stable molecular wires, which provides a unique opportunity for charge transfer processes. Consequently, the electroanalytical sensing of AML was explored at bare/unmodified and DNA-modified SPEs in a linear range between 0.066–1.0 µM and 0.066–2.0 µM with the detection limit (3) found to be 20.70 nM and14.94 nM, whilst corresponding sensitivities of: 0.43 A L mol-1 and 4.23 A L mol-1 respectively. Although, the superior electrochemical signature of bare SPEs is evident, the immobilization of DNA onto SPEs enhances the sensitivity 10-times more than the bare SPEs. Furthermore, the optimized electroanalytical protocol using the unmodified SPEs, which requires no pre-treatment and electrode modification step, was then further applied to the determination of AML in real samples.