The most effective way to minimize the undesirable side effects of an overdose and to maximize both therapeutic benefits and patient compliance is through TDDS. Due to first-pass metabolism, clotrimazole possesses antifungal action and a half-life of two hours. It has to be dosed frequently. Betamethasone Dipropionate gives anti-inflammatory effect to reduce symptoms of candidiasis. To prolong the release, increase the drug's bioavailability, and increase patient compliance, a transdermal patch containing Clotrimazole and Betamethasone Dipropionate was developed. By adjusting the polymer concentrations through the solvent casting process, various formulations were created. The generated formulations conducted evaluations for several factors, including drug excipient compatibility, drug content, thickness, weight variation, folding durability, moisture uptake, moisture loss, and in vitro drug release. A 32 complete factorial design was used to examine the impact of various polymer concentrations on the reactions of clotrimazole and betamethasone dipropionate, including moisture uptake and percentage of medication released in 12 hours. To determine the kinetics of drug release, in vitro release data were fitted to various models. Batch F5 was considered optimum batch which contained HPMC K4M and Eudragit L-100 in concentrations of 350 and 250 mg respectively. For clotrimazole and betamethasone dipropionate, formulation F5 was shown to have the maximum drug release 75.91% and 67.09%, respectively. The created F5 had the highest drug content, with clotrimazole and betamethasone dipropionate concentrations of 98.78% and 98.82%, respectively.