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Objectives 3D printed polymeric film intended for topical delivery of berberine (BBR) was developed using stereolithography (SLA) to enhance its local concentrations. PEGDMA was utilized as photopolymerizing resin, with PEG 400 as an inert component to facilitate BBR solubilization and permeation. Methods Three batches of topical films were printed by varying resin and PEG 400 compositions. In-vitro physicochemical characterizations of the 3D printed films were performed using several analytical techniques including ex-vivo drug permeation studies. In-vivo skin irritation studies were also conducted to assess the skin irritation potential. Key findings Films were 3D printed according to design specifications with minimal variations. Microscopic analysis confirmed 3D architecture, while thermal and X-ray diffraction studies revealed amorphous BBR entrapment. Drug permeation study showed effective ex-vivo diffusion up to 344.32 ± 61.20 µg/cm2 after 24.0 h possessing a higher ratio of PEG 400. In-vivo skin irritation studies have suggested the non-irritant nature of printed films. Conclusions Results indicated the suitability of SLA 3D printing for topical application in the treatment of skin diseases. The presence of PEG 400 in the printed 3D films facilitated BBR diffusion, resulting in an improved flux in ex-vivo model and non-irritant properties in vivo. [ABSTRACT FROM AUTHOR]