This work deals with fast-dissolving drug delivery systems of meloxicam (MX) derived from electrospun polyvinylpyrrolidone (PVP)/2-hydroxypropyl--cyclodextrin (HPCD) nanofiber mats. Electrospinning of solutions with different solvent systems [dimethylformamide (DMF) and ethyl alcohol (EtOH)] was performed. Prepared films were evaluated for morphology, physical, and mechanical properties. MX content, dissolving time, MX release, and cytotoxicity of films were investigated. In vivo studies were also performed in healthy human volunteers. The results showed that MX/HPCD complexes improved the solubility of MX. PVP also increased MX solubility and the stability of MX/HPCD complexes. Films were successfully prepared by two solvent systems with fiber in the nanometer range. MX was well incorporated into the films (100% efficiency). The X-ray patterns and DSC experiment indicated an amorphous form of MX. A fast disintegration time and burst release of MX was obtained from EtOH system. Cytotoxicity testing of the films produced by EtOH system proved safer than the DMF system. In vivo studies revealed that films rapidly dissolved in the mouth and had a less bitter taste than MX. These results suggest that electospun films from EtOH system may be a good candidate for fast-dissolving drug delivery systems to increase palatability of dosage forms.