AbstractRecently, in vitro models emerge as valuable tools in biomedical research by enabling the investigation of complex physiological processes in a controlled environment, replicating some traits of interest of the biological tissues. This study focuses on the development of tubular polymeric scaffolds, made of electrospun fibers, aimed to generate three‐dimensional (3D) in vitro intestinal models resembling the lumen of the gut. Polycaprolactone (PCL) and polyacrylonitrile (PAN) are used to produce tightly arranged ultrafine fiber meshes via electrospinning in the form of continuous tubular structures, mimicking the basement membrane on which the epithelial barrier is formed. Morphological, physical, mechanical, and piezoelectric properties of the PCL and PAN tubular scaffolds are investigated. They are cultured with Caco‐2 cells using different biological coatings (i.e., collagen, gelatin, and fibrin) and their capability of promoting a compact epithelial layer is assessed. PCL and PAN scaffolds show 42% and 50% porosity, respectively, with pore diameters and size suitable to impede cell penetration, thus promoting an intestinal epithelial barrier formation. Even if both polymeric structures allow Caco‐2 cell adhesion, PAN fiber meshes best suit many requirements needed by this model, including highest mechanical strength upon expansion, porosity and piezoelectric properties, along with the lowest pore size.