This preprint reports electrochemical sensing of the antihypertensive drug reserpine using ready-to-use carbon black–polylactic acid (CB/PLA) 3D-printed electrodes. Experimental and computational analyses demonstrate that polylactic acid enhances sensing performance without requiring post-printing activation. Under optimized conditions in acetate buffer (pH 5), the sensor exhibits a wide linear range of 0.05–53.6 μM, a low detection limit of 24 nM, and recoveries of 98–105% in artificial blood samples. The work provides a simple, cost-effective, and reliable platform for sensitive determination of reserpine in biological matrices.