The research manuscript’s objective is to develop transdermal patch formulations of Diclofenac potassium utilizing different ratios of Eudragit L-100D (hydrophobic) and Pluronic F-127(hydrophilic) polymers and Amomum subulatum leaf oil as a ‘penetration enhancer’. In this study, several physical parameters, including moisture content, moisture uptake, tensile strength, flatness, folding endurance, uniformity, weight variation, and thickness were assessed. Formulations were prepared by the solvent evaporation technique after an interaction study between polymers and penetration enhancers. Additionally, the transdermal patches were studied for physicochemical parameters involving permeation studies, mechanical properties, and toxicity studies of skin irritation. Formulations exhibited favourable pre-formulations and post-formulary characteristics. ‘In vitro permeation’ was conducted using an USP type-7 dissolution apparatus. The patches demonstrated an apparent absence of potentially harmful skin irritation. Experimental results indicated a controlled and sustained administration of the medicament from the formulation with an increasing proportion of hydrophilic polymer and permeation enhancers with reduced toxicity. The study concludes that Diclofenac potassium can be effectively developed into transdermal patches using Amomum subulatum leaf oil as a penetration enhancer for enhanced permeation and sustained drug administration.