Doxycycline (DOXY), a widely used antibiotic during COVID-19, was overused, leading to concerns about contamination of aquatic environments and environmental problems. The present study used the Ti/TiO2-RuO2-IrO2 electrode for DOXY's electrochemical oxidation (EO) in batch and once-through continuous mode operations. Process parameters were optimized using a response surface methodology (RSM)-Box-Behnken Design (BBD) model. The impact of key input parameters, including time (t), current density (j) (mA/cm2), and pH, on the percentage of DOXY degradation and energy consumption was systematically investigated. Under optimal conditions pH = 3, t = 73 min, and j = 11.63 mA/cm2, DOXY degradation achieved 91% with an energy consumption of 5.283 kWh/m³. In the once-through continuous mode EO process, optimal conditions reached 91% DOXY degradation with an energy consumption of 13.98 kWh/m³, achieved at a residence time (Rt) of 139 min, elapsed (Et) time of 100 min and at j = 20.40 mA/cm2. The EO process utilizing Ti/TiO2-RuO2-IrO2 electrodes demonstrates significant potential for the degradation of DOXY, primarily due to its enhanced degradation efficiency. This method's superior performance highlights its viability as a highly effective approach for the treatment of DOXY-contaminated wastewater.