The aim of the present study is to formulate the cyclodextrin based topical Gel of Dapsone and Adapalene as antibacterial agent for the treatment of acne. The uniqueness of Dapsone, 4,4′-diaminodiphenylsulfone (DPS) is attributed to its dual antimicrobial and anti-inflammatory effects. Nevertheless, DPS limited solubility in water makes its topical formulation for treatment of dermatological conditions effective at higher percentage. The interaction between DPS and Hydroxypropyl β-cyclodextrin (Betadex®) in the solution state was investigated using phase solubility technique. Dapsone and Adapalene combination gel formulated using different gelling agent and solubilizers. All the formulation was developed by quality by design approach (QBD), which requires a multivariate approach for understanding the multifactorial relationships among formulation parameters. All the formulation was found to be physically stable and efficacious when compared with marketed product. Cyclodextrin used as complexing agent which enhanced the solubility of Dapsone within the formulation thus avoids recrystallization and improves the efficacy with use of optimum percent of Dapsone within the formulation. To assess the efficacy of prepared gel for anti-acne activity, Ex vivo Antibacterial studies, Cumulative release studies through vertical diffusion cell. Dapsone and Adapalene gel showed potent antibacterial activity for P. acne strain through the cylinder plate technique. The Adapalene and Dapsone gel combination product using Cyclodextrin could be the cost-effective product due to use of optimum concentration of Dapsone in solubilized form over the marketed products which have high percent of Dapsone and are gritty in appearance.