Herein, we have fabricated silver (Ag) over selenium (Se) to explore its enriched electrochemical performance towards the simultaneous detection of nitro-aromatic drugs (nitrofurantoin (NFT) and P-nitrophenol (P-NP)). Due to its synergistic effect, Ag/Se modified GCE showed excellent electro-catalytic activity compared to other electrodes. Well-defined and divergent reduction peaks were obtained at −0.49 V (NFT) and −0.85 V (P-NP) with a detection range of 0.9 V at Ag/Se/GCE. It withholds an extensive linear range of 0.1 to 210 µM for NFT and 0.1 to 150 µM for P-NP with a nanomolar level detection limit of 23.87 nM L−1 & 7.82 nM L−1; an appraisable sensitivity of 1.138 µA µM−1 cm−2 & 2.86 µA µM−1 cm−2 for NFT and P-NP, respectively. Interestingly, the electrode possesses a high selectivity in the presence of biomolecules, nitro drugs, and metal ions. Examination of nitro-aromatic drug contamination on water sources shows a massive peril to human life and marine environs due to its adverse hazardous effects. Further, the fabricated Ag/Se-based electrochemical sensor was exposed to various environmental aqueous samples to detect NFT& P-NP which has demonstrated an exquisite recovery results in practical feasibility. Thereby confirms that Ag/Se-based electrochemical sensors have boundless potential for ecological investigations and sensing applications.