<p>Molecularly imprinted polymers (MIPs) pave the way for developing reliable sensors, enabling the design of artificial receptors with excellent selectivity and environmental friendliness. In this study, a combination of computational and experimental approaches was achieved to design a polypyrrole-based molecularly imprinted electrochemical sensor for bisphenol A (BPA) detection in aqueous media. Density functional theory (DFT) simulations were performed to identify the most suitable crosslinker among three candidates known for their strong affinity toward BPA: ethylene glycol dimethacrylate (EGDMA), 1,3,5-tris(4-aminophenyl) benzene (TAPB), and N, N’-methylene-bis-acrylamide (MBAA). The calculated interaction energy values were found comparable, but MBAA was chosen due to its ability to stabilize the polypyrrole matrix, its hydrophilic nature, and its solubility in eco-friendly solvents. Based on this finding, a BPA-MIP-based electrochemical sensor was designed and characterized. It exhibited a low detection limit (1 nM) and a high sensitivity of (9.66 ± 0.86) µA/µM. The dissociation constant (K_d), which quantifies the imprints/analyte’s affinity, was calculated by modeling the calibration curve with a one-site binding-Hill model. Kd was of order of (2.05 ± 0.18) × 10^− 9 M. Selectivity tests were investigated using bisphenol S, biphenyl, salicylic acid, and paracetamol to assess the sensor’s selectivity. Results showed that the designed device could effectively distinguish BPA from these analogs, confirming its specificity and suitability for detecting BPA even in complex sample matrices. </p> Graphical abstract <p></p>