The widespread use of antibiotics in humans and animals has resulted in the accumulation of their residues in food and the environment, posing significant threats to human health, the environment, and the global economy. Herein, we have developed a highly sensitive and selective electrochemical sensor by integrating gold-silver alloy nanocoral clusters (Au-Ag-ANCCs) with reduced graphene oxide (r-GO) and poly(L-histidine) composites at the surface of glassy carbon electrode (GCE). The developed sensor (Au-Ag-ANCCs/r-GO/poly(L-histidine)/GCE) was designed for the simultaneous determination of vancomycin (VAN) and ceftriaxone (CFT) residues in food samples. Its morphological and electrochemical properties were exhaustively examined using UV–Vis spectroscopy, FT-IR, XRD, SEM, EDX, EIS, and CV. The sensor showed exceptional performance in a linear range of 1.0 pM to 120 μM for VAN and 1.0 pM to 290 μM for CFT. The limits of detection were 0.11 pM for VAN and 0.017 pM for CFT, while the limits of quantification were 0.36 pM for VAN and 0.057 pM for CFT. The sensor exhibited remarkable reproducibility, repeatability, stability, and selectivity. It was successfully applied to detect VAN and CFT residues in chicken meat, fish, and milk, achieving recoveries of 96.2–102.1 % with relative standard deviation (RSD) below 5 %. Therefore, the sensor is an ideal tool for addressing the global antibiotic residue crisis in food samples.