Due to the toxicity of mercury, an alternative electrode has to be constructed still having the unique properties of mercury electrode. Thus, mercury meniscus modified silver amalgam electrode (m-AgSAE) was constructed to overcome this problem and to be the suitable replacement commercial mercury electrode. The voltammetric behavior of antibiotic drugs (ampicillin and penicillin G) had been studied using m- AgSAE with Ag/AgCl (3M KCl) as the reference and the measurement was conducted in Britton-Robinson buffer (BRB). Differential pulse voltammetry (DPV) and adsorptive stripping voltammetry (AdSV) techniques were used to conduct these studies. This study was done to observe and study the capability of m-AgSAE properties that can match with commercial mercury electrode. The optimal conditions for ampicillin and penicillin G determination were successfully evaluated in the concentration range of 10 μmol/L to 90 μmol/L. The limits of detection for ampicillin and penicillin G at m- AgSAE were found to be 3.8 μmol/L and 2.5 μmol/L respectively. Using the optimum conditions, the practical application of the newly developed method has been verified on the determination of ampicillin and penicillin G in spiked samples of drinking and river water. © 2018 World Research Association. All rights reserved.