Transdermal (TD) route of diltiazem hydrochloride (DH) administration attracts ample attraction, but remains strenuous due to slower penetration of drug across the skin. In the present investigation, we studied the possibility of using gold nanoparticle (GNP) to enhance the skin permeation of DH. A novel TD device was fabricated from polyelectrolyte complex (PEC) reinforced with nanogold-nanocellulose (GNP-NC) composites and characterized using NMR, FTIR, XRD, TEM and SEM. The PEC membrane was designed using the electrostatic interaction between cationic guar gum (CGG) and borate modified poly(vinyl alcohol). The hybrid filler deposited films have been prepared at different loading levels and the influence of loading on drug encapsulation efficiency, tensile properties, thermal stability, water vapor permeability, and skin permeability were evaluated. The effect of storage time and temperature on the drug release behavior was investigated. The devices were also examined for in vivo skin adhesion and irritation in human subjects, cell viability and environmental fitness to assess its application in pharmaceutical field. The results of the investigation suggested that the developed film may serve as a potential device for the TD delivery of DH.