As atenolol overdosing can lead to severe health complications, the rapid detection of atenolol intake in point-of-care settings is highly desirable. The recent advancement of redox analytical methodologies has facilitated the efficacious quantification of these compounds for drug analysis, but their performance still presents challenges in practical applications. This study addresses these challenges by controlling the electropolymerization of polydopamine (PDA) on highly porous laser-induced graphene (LIG) electrodes with enhanced electrochemical redox activity for the detection of drug molecules such as atenolol, with minimized interference with the other active substances to induce variation of electrochemical behavior. The enhanced sensitivity of atenolol is attributed to the superhydrophilicity and increased number of active surface sites and -NH2 groups in the PDA polymer through a controlled polymerization process. Moreover, the simulation results further reveal that highly sensitive sensing of atenolol molecules relies on optimal adsorption of the atenolol molecule on dopamine or dopaminequinone structural units. The resulting sensors with high repeatability and reproducibility can achieve a low detection limit of 80 μM and a sensitivity of 0.020 ± 0.04 μA/μM within a linear range from 100 to 800 μM. The materials and surface chemistry in the electrode design based on highly porous LIG provide insights into the integration and application of future scalable and cost-effective electrochemical sensors for use in point-of-care or in-field applications.