Objective: India is referred as goldmine of herbal drugs but still lack of optimization of herbal drugs, which has kept us on the back foot. The rationale of the study is to prepare optimized transdermal drug delivery system of curcumin employing response surface methodology to study the collective effect of independent variables like concentration of ethyl cellulose, hydroxyl propyl methyl cellulose and dibutyl phthalate which significantly influenced characteristics like percentage elongation and in vitro drug release. Method: Twenty formulations containing varying concentrations of polymers and permeation enhancer were prepared using solvent casting technique. Result: The study revealed that the effect of dibutyl phthalate (DBP) concentration was the highest on percentage elongation (P < 0.0001), while hydroxy propyl methyl cellulose (HPMC) concentration exhibited pronounced effect on drug release (P < 0.0001) through dialysis membrane. Linear model fitted the best for curcumin release and elongation for all formulations. According to Derringer's desirability prediction tool, the composition of optimized film was found to be 242.14% of HPMC, 109.59% of ethyl cellulose (EC), and 1.03% of DBP. Under these conditions, the optimized patch exhibited a predicted value of %elongation and in vitro drug release of 94.35% and 80.0306%, respectively, which was comparable to the actual values of percent elongation and in vitro drug release i.e. 95.02% and 81.03% respectively. FTIR and thermal studies were also performed which revealed no interaction or complexation between drug and excipients. The ex vivo study performed using rat skin showed that the cumulative drug release from the optimized patch showed flux of (30.68 ± 18) µg/cm