<p>Polymorphism plays a critical role in the pharmaceutical industry, influencing drug solubility, stability, and bioavailability. This study focuses on the solvent-mediated transformation of clopidogrel bisulfate from polymorphic form II to the more stable and pharmaceutically preferred form I to enhance its therapeutic efficacy. Comprehensive characterization using XRPD, FT-IR, UV–Vis, confirmed successful conversion and improved crystallinity. Notably, whereas prior electrochemical characterizations of clopidogrel polymorphs employed gold electrodes, this work is the first to utilize nickel‐foam electrodes. The Ni‐foam platform produced even more pronounced voltametric signals comparable in profile but with higher peak currents and lower over potentials than those recorded on gold underscoring its superior sensitivity for assessing polymorph‐specific redox behaviour. Theoretical studies employing DFT at the B3LYP/6–311 + G (d, p) level provided insights into molecular geometry, stability, and reactivity. Thermodynamic and FMO analyses further supported the electronic stability of form I. Hirshfeld surface analysis quantified key intermolecular contacts, revealing prominent hydrogen-bonding and π–π interactions that stabilize the crystal lattice. Molecular docking with the P2Y12 receptor (4NTJ) revealed a strong binding affinity (− 6.9&#xa0;kJ·mol⁻¹), suggesting effective antiplatelet activity. Furthermore, this work establishes a cost-effective, solvent-mediated three-step strategy for controlling polymorphic transformation. By coupling redox analysis, stability profiling, charge transfer studies, and molecular docking, the approach ensures reproducible yield of the pharmaceutically superior form I. This reproducibility directly enhances the manufacturing reliability, therapeutic consistency, and cost-effectiveness of clopidogrel’s formulations.</p>