Thymoquinone (TQ) has demonstrated various dermatological effects that could be effectively used for the treatment of many conditions like psoriasis. Clinical applications of thymoquinone are limited, owing to its low bioavailability due to low solubility and permeability. Therefore, a new transdermal drug delivery system is needed to overcome problems of TQ delivery. The aim of this work was to develop and evaluate transdermal patches for prolonged delivery of thymoquinone using Eudragit E polymer, plasticizers, and Aloe Vera (AV) as penetration enhancer. Novel TQ loaded nanocapsules (NCs) were developed using L-arginine based poly amide (TQ/ Arg-PA) using interfacial polymerization technique, which was incorporated into the matrix transdermal patch as a potential treatment of psoriasis. The resulted nanocapsules were characterized by NMR, FTIR to confirm the structure. Optimal TQ nanocapsules containing formulation showed high entrapment efficiency of TQ (99.60%). Molecular and thermal profiling using FTIR, NMR, DSC, TGA, XRD and TEM for both of TQ/Arg-PA and the transdermal patch revealed the effective development of a spherical nanocapsules (NCs) with an average particle size of 129.23 ± 18.22 nm. DSC and XRD analysis showed that the Arg-PA processed and amorphous to semicrystalline shape that encapsulate TQ. Using Franz diffusion cells and synthetic membrane the in vitro release profile of the prepared patches demonstrated an extended release of TQ over 24 hours, therefore ensuring its suitability as transdermal patches with sustained release. In conclusion, the produced formulation can be a potential substitute for commonly used corticosteroids and other drugs; due to its effectiveness, safe, and lack of the side effects commonly reported by other drugs.