The present investigation highlights the formulation and characterization of transdermal patch of Acyclovir using Artocarpus heterophyllus lam mucilage as a natural polymer. The jackfruit mucilage was obtained from ripen fruit pulp of Artocarpus heterophyllus lam belonging to family Moraceae. The mucilage was isolated by maceration technique. The mucilage was characterised for purity, pH of mucilage, swelling index, ash value, Angle of repose, true density, bulk density, tapped density, Hausner’s ratio and Carr’s consolidation index. The films were prepared by solvent casting method and optimized by using 32 full factorial design and evaluated for physical parameters such as flatness, folding endurance, thickness, tensile strength, moisture content, moisture uptake, skin irritation potential of polymer matrices. The factorial design gave the 9 batches, depending on the desirability the solutions generated by the expert design the F1 batch was selected and there results of thickness (0.57 ± 0.0057 mm), folding endurance (311 times), %drug content (98.06 ± 0.02%), In-vitro drug release (95.26 ± 0.046%), Moisture content (7.53 ± 0.01%), Surface pH (6.38±0.058), Swelling index (7.13 ± 0.01), Tensile strength 24.88 ± 0.16 (N/25.4 mm). The transdermal patch using jackfruit mucilage shows the 100 % flatness. Thus from the present work it can be concluded that the Jackfruit mucilage can be a promising polymer for the film formation and thus should be explored in future as an inert suitable pharmaceutical excipient.