The oral mucosa is a promising absorption site for drug administration because it is permeable, highly vascularized and allows for ease of administration. Nanofiber scaffolds for local or systemic drug delivery through the oral mucosa, however, have not been fully explored. In this work, we fabricated electrospun gelatin nanofiber scaffolds for oral mucosal drug delivery. To improve structural stability of the electrospun gelatin scaffolds and allow non-invasive incorporation of therapeutics into the scaffold, we employed photo-reactive polyethylene glycol diacrylate (PEG-DA575, 575 gmol-1) as a cross-linker to stabilize the scaffold by forming semi-interpenetrating network gelatin nanofiber scaffolds (sIPN NSs), during which cross-linker concentration was varied (1x, 2x, 4x and 8x). The results showed that electrospun gelatin nanofiber scaffolds after being cross-linked with PEG-DA575 (i.e. sIPN NS1x, 2x, 4x and 8x) retained fiber morphology and possessed improved structural stability. A series of structural parameters and properties of the cross-linked electrospun gelatin scaffolds were systematically characterized in terms of morphology, fiber diameter, mechanical properties, porosity, swelling and degradation. Mucin absorption onto sIPN NS4x was also confirmed, indicating this scaffold possessed greatest mucoadhesion properties among those tested. Slow release of nystatin, an anti-fungal reagent, from the sIPN gelatin nanofiber scaffold was demonstrated.