Risperidone (RIS) is one of the most prescribed atypical antipsychotics approved for the treatment of various neuropsychiatric diseases. For the correlation of serum concentration and pharmacological effects of RIS, therapeutic drug monitoring is considered a fundamental concept for clinical application. This paper is provided to develop an electrochemical probe for the determination of RIS in biological samples by modification of glassy carbon electrode (GCE) using gold nanoparticles (AuNPs) and iron metal-organic-frameworks (FeMOFs). This probe fabrication process was characterized with various techniques including Fourier transform infrared (FTIR), emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX), atomic force microscopy (AFM), and dynamic light scattering (DLS) to confirm the proper synthesis of materials and the sensors designing. The developed probe square-wave voltammetry (SWV) signal was linear upon RIS concentration from 0.02 to 50 mu g/mL with a low limit of quantification (LOQ) of 0.02 mu g/mL. Based on the validated method, high accuracy and precision, good specificity, and suitable stability of fabricated probes were achieved. As the ultimate step, this method was successfully applied for the quantification of RIS in patients' plasma samples with regular RIS consumption. The fabricated electrochemical demonstrates favorable clinical applicability due to its simplicity, high sensitivity, low sample pretreatment time, and rapid analysis time, making it a promising probe as an alternative to current separation-based methods. Also, the developed probe is cost-effective, as it uses a low amount of materials, decreases sample processing time, and utilizes inexpensive materials, which could remarkably reduce the overall cost of RIS concentration detection in clinical samples. The obtained results showed the potential of the developed probe for fast and reliable detection of RIS in plasma samples.