Modern electrochemical sensor design involves ongoing modifications and enhancements in surface kinetics, leading to devices with improved analytical performance, reliable outcomes, and enhanced applications. Extensive research has been devoted to screen-printed electrode (SPE) based sensors as electrochemical sensors for drug determination with high sensitivity, particularly suitable for surface modification. The combination of carbon nanomaterials, noble metals, and polymers has led to promising improvements in the electroanalytical performance of sensors. These materials possess unique chemical and physical properties contributing to exceptional electrode reactivity. Our research focuses on modifying screen-printed electrodes using a synthesized electroconductive polymer-based nanocomposite ink to enhance the sensitivity of detecting low concentrations of doxorubicin (DOX) in a simulated biological matrix. Commercial carbon screen-printed electrodes were used as a substrate for modification. The ink was synthesized using a composite material based on reduced graphene oxide and 0.5 wt.% Au nanoparticles (rGO + 0.5 wt.% Au NPs), synthesized using a two-step method involving the reduction of graphene oxide and the decoration of the reduced graphene flakes with gold nanoparticles. All electrochemical measurements were performed using cyclic voltammetry in 25 mL 0.1 M phosphate-buffered saline (pH 7.0) by adding DOX (2 mg/mL) in portions ranging from 10 to 150 μL. The modified electrode exhibited a superior electrochemical response to DOX, lower detection limit, and higher sensitivity and electrical conductivity than the commercial one.