Background: The study aimed to develop an antiarthritic gel formulation incorporating drug-loaded mesoporous silica nanoparticles (MSNs) for targeted and controlled drug delivery. The selection of MSNs was based on their high surface area, tunable pore size, and controlled release capabilities. Carbopol 940 was chosen as the gelling agent due to its compatibility and viscosity properties. Methodology: The gel was formulated by dispersing Carbopol 940 in distilled water, followed by hydration and pH adjustment. Drug-loaded MSNs were incorporated into the gel base with continuous stirring and sonication. Formulation parameters such as viscosity, spreadability, texture, particle size, and drug release were optimized. Results & Discussion: The optimized gel exhibited desirable viscosity, spreadability, and texture properties. Particle size analysis indicated a narrow size distribution, and zeta potential measurements confirmed stability. In vitro drug release studies showed sustained release for both Methotrexate and Tofacitinib Citrate. Ex vivo permeation studies demonstrated efficient skin penetration, supporting the potential of the gel for transdermal drug delivery.