This work focuses on applying a combined process combining electro-Fenton (EF) pretreatment with biological degradation to mineralize the antiviral Ribavirin in an efficient, economical and ecological manner. First, the main experimental parameters affecting the efficiency of the electro-Fenton process, namely applied current intensity, Fe(II) catalyst concentration and initial Ribavirin concentration were evaluated and optimized. Indeed, the mineralization rate reaches maximum residual values of 99% after 4 hours of electrolysis applying a current of 200 mA. This mineralization is accompanied by an increase in biodegradability, evaluated from the BOD₅/COD ratio, which goes from 0.04 at the beginning of treatment (1 h) to 0.45 after 2 hours of electrolysis, demonstrating the feasibility of a biological treatment. In addition, the energy efficiency decreased when the treatment time was extended due to the limitation of mass transport. Thus, the feasibility of coupling electro-Fenton and biological treatment has been successfully demonstrated on a laboratory-scale was, achieving a 96.66% removal rate by the Bio-EF process. A Box-Behnken design based on response surface methodology was applied to develop a model for predicting Rib removal rate. The interaction of factors such as Rib concentration (X₁), catalyst concentration (X₂) and electrolysis time (X₃) was analyzed to identify optimal operating conditions. The model results obtained are statistically significant with an R² of 0.99, indicating that the proposed model is significant and relevant. In addition, the iso-response curves obtained enabled us to determine the optimal experimental conditions required for effective mineralization of the targeted antiviral.