A fluorescence probe based on iron oxide quantum dots (IO-QDs) was synthesized using the hydrothermal method for the determination of tetracycline (TCy) and ciprofloxacin (CPx) in aqueous solution. The IO-QDs were characterized using high-resolution transmission electron microscopy (HR-TEM), powder X-ray diffraction (P-XRD), vibrating sample magnetometry (VSM), and Fourier-transform infrared spectroscopy (FTIR). The as-prepared IO-QDs are fluorescent, stable, and with a fluorescence quantum yield (QY) of 9.8 ± 0.12%. The fluorescence of IO-QDs was observed to be quenched and enhanced in the presence of TCy and CPx, respectively. The fluorescence intensity ratio shows linearity at concentrations from 1-100 μM and 5-100 μM for TCy and CPx, respectively; the detection limit for TCy and CPx was estimated to be 0.71 μM and 1.56 μM, respectively. The proposed method was also successfully utilized in the spiked samples of drinking water and honey with good recoveries. The method offered convenience, rapid detection, high sensitivity, selectivity, and cost-efficient alternative options for the determination of TCy and CPx in real samples.