This study developed biodegradable drug-eluting anti-adhesive poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous films for surgical wounds via a co-axial electrospinning technique. After spinning, the properties of the co-axially spun membranes were characterized by scanning electron microscopy, laser-scanning confocal microscopy, Fourier Transform Infrared spectrometry, water contact angle measurements, and tensile tests. Furthermore, a high-performance liquid chromatograph (HPLC) analysis and an enzyme-linked immunosorbent assay (ELISA) evaluated the in vitro and in vivo release curves of lidocaine and hEGF from the films. PLGA anti-adhesion nanofibers eluted high levels of lidocaine and hEGF for over 32 and 27 days, respectively, in vitro. The empirical outcomes suggested that the anti-adhesive nanofibrous films with extended release of drugs offer post-operative pain relief and wound healing.