ABSTRACT: Aceclofenac is classified as a BCS Class II drug because of its low water solubility. Systemic adverse effects, such as anticoagulant effects, have been described when SRP is taken orally. The goal of this study was to see how well a topical Niosomal gel containing Aceclofenac (ACE) and Serratopeptidase (SRP) could deliver the drugs. Particle size, shape, entrapment efficiency, and in vitro properties of Niosomal formulations produced using the thin film hydration process at varied cholesterol and Span 40 ratios were studied.The average particle size of the Niosomal formulation was determined to be between 1 µm – 2µm. The entrapment efficiency of the Niosomal formulations F2 (1:1:1) and F6 (1: 2: 1) of cholesterol and surfactant was 65 percent and 66.4 percent, respectively. Niosomal formulation (F2 and F6) displayed high percentage of drug release after 12 hr. For the convenience of application, greater stability, reduced aspect effects, greater affected person compliance, and the convenience of discontinuation on desire, there were numerous advantages to deliver ACE through topical route. Therefore, topical therapy isn’t most effective promising at the protection and efficacy fronts however additionally at the financial fronts too. Niosomal gel had greater pores and skin penetration, according to an in vitro study results.