Background: Due to their optimal mechanical and biological properties, nanofibers have numerous medical applications. Electrospinning is one of the widely used techniques for generating drug-containing nanofibers. Objectives: The aim of this study was to assess the use of the electrospinning method to prepare fast-dissolving loratadine nanofibers. Materials and Methods: Polyvinylpyrrolidone (PVP) nanofibers containing loratadine were produced using the electrospinning method. A full factorial design was employed to evaluate the formulations, including the four following variables: the concentration of PVP, the ratio of drug to polymer, the feed rate, and the voltage applied at two levels. After preparing the samples, assessments were carried out using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC). Dissolution tests and determination of the time of disappearance were also carried out. It was observed that reducing the concentration of polymer, reducing the feed rate, and increasing the voltage applied to the polymeric solution up to an adequate amount allowed the possibility of creating nanofibers with a smaller diameter and greater uniformity. Results:The results showed that the fiber diameter and the amount of loratadine affected the drug release and the disappearance time of nanofibers. The smaller the fiber diameter and drug amount, the faster the solubility and the release time of nanofibers. Conclusions: It was concluded that electrospinning can be a suitable method for preparing fast-dissolving loratadine nanofibers.