<p>The most commonly used antibiotic for bacterial infections in human medicine is amoxicillin (AM). The pharmaceutical industry’s effluents can be hazardous to the environment and the general public due to their widespread use in several illnesses, including rashes, pneumonia, vomiting, tonsillitis, bronchitis, and sinusitis and excessive application of AM. For the detection and identification of AM in drugs, biological fluids, environmental pollutants and foods, the new electroanalytical method is needed with excellent sensitivity and cheap implementation. We have developed a novel multifunctional, cost-effective sensor that quantifiably and analytically detects amoxicillin using an enzyme less free-standing nickel hydroxide@ poly(meta-aminophenol)/ nickel foam (NH@PmAP/NF). Due to the synergistic effect of metal hydroxide and conducting polymer, our proposed electrode showed increased electrochemical activity, improved electron transfer rate, and a higher electroactive surface area. Various analytical techniques were utilized for evaluating the morphological, structural, and electrochemical characteristics of nanostructured materials. An electrocatalytic role of NH@PmAP/NF has been demonstrated in the oxidation process of AM with a wide concentration range of 0.05 to 400 µM, lower detection limit of 2.28 nM and an outstanding sensitivity 90.74 μA μM⁻¹ cm^-2. The as-fabricated electrode has been fruitfully applied to the determination of amoxicillin in cow milk, and drinking water samples, with results compared to standard methods of high-performance liquid chromatography (HPLC) with reasonable recovery rates.</p> Graphical Abstract <p></p>