Transdermal patches are a convenient drug delivery system that can provide a constant therapeutic effect over a prolonged period. The use of natural plant extracts in transdermal patches has been gaining attention due to their potential therapeutic benefits and fewer side effects. This study aims to formulate, optimize, and evaluate transdermal patches of Eclipta alba leaf extract. The Eclipta alba leaf extract was prepared by maceration using ethanol as a solvent. The extract was then incorporated into the transdermal patch matrix, which consisted of a mixture of HPMC K4, HPMC K15 and polyethylene glycol 400. The patches were prepared by the solvent evaporation method, and the patch thickness was optimized using a 32 factorial design. The optimized patches were evaluated for physicochemical characteristics, in vitro release, and skin irritation potential. The optimized transdermal patches had a thickness between 0.112±0.01 and 0.154±0.01mm, and the weights ranged between 7.10±0.75mg to 7.96±0.75mg. The release of the Eclipta alba leaf extract was sustained over 24 hours. The patches showed good skin irritation potential, as evidenced by the absence of erythema or edema on the skin. The physicochemical characteristics of the patches, such as weight variation, drug content, and moisture content, were within the acceptable limits. The study successfully formulated, optimized, and evaluated transdermal patches of Eclipta alba leaf extract. Transdermal patch (F5) didn't cause any noticeable signs of irritation or edema on rat skin. Transdermal patch (F5) shown a good anti-inflammatory activity comparative to the marketed formulation in carrageenan-induced paw edema model.