In this study, ZnFe2O4-based nanostructures, including ZnFe2O4 nanoparticles and ZnFe2O4/ZnO nanocomposite, were introduced on screen-printed electrodes surface (SPEs) for enhancing the selective electrochemical signals towards the chloramphenicol (CAP) and furazolidone (FZD) antibiotics. The difference in the molecular structure of CAP and FZD leads to significant changes in adsorption capacity and electron transfer kinetic at modified electrodes. Interestingly, FZD antibiotic with formal reduction potential (E0’) near the Fermi level of ZnFe2O4-based nanostructures showed a strong dependence of electrochemical response with electron transfer kinetic. In contrast, CAP antibiotic with E0’ away from the Fermi level of ZnFe2O4-based nanostructures showed the high sensitivity of electrochemical response with the electroactive surface area of modified electrodes. The obtained results might offer the basis to develop a suitable approach for improving the analytical performance of advanced spinel oxide nanostructures-based electrochemical sensing devices. Under optimal conditions, ZnFe2O4/ZnO/SPEs enabled the simultaneous monitoring of CAP and FZD in the linear working ranges of 0.5–100 μM and 0.5–75 μM with high electrochemical sensitivity of 1.87 and 1.82 μA μM−1 cm−2, respectively. The ZnFe2O4-based electrochemical nanosensor exhibited high repeatability and long-term storage stability for simultaneous analysis of CAP and FZD in milk sample.