The present research work was aimed to develop a novel gel for Tacrolimus to enhance the drug absorption by the topical application, which overcomes the demerits of oral dosage form and conventional gel system of Tacrolimus . The gels were prepared with carbopol 934 as a gelling agent used in six different concentrations. Span 20 and Tween 20 were included as emulsifying agents in two different concentrations. Liquid paraffin was used as an oil phase, and methyl and propyl paraben were included as preservatives. Ethanol was used to dissolve the drug for preparing the aqueous phase and Triethanolamine was added at the end of preparation, as quantity sufficient for pH adjustment. All the formulated nanogels were screened for the parameters, namely, appearance, pH, viscosity study, Spreadability, swelling index, drug content, and in vitro drug release studies. The optimized formulation ActG-4 showed 81.95% of drug release up to 8 h, and the particle size analysis reported good size range, and the gel was found to be nonirritant and nontoxic which was confirmed by HET CAM test. Tacrolimus can be successfully formulated as gel for better-sustained effect and can be a suitable alternative approach to the oral dosage forms for the management of Psoriasis.