Rosuvastatin calcium is a member of statins that lowers low-density lipoprotein levels and raises levels of high-density lipoprotein by inhibiting 3-hydroxy 3-methyl glutryl co-enzyme A (HMG-COA) reductase. It was primarily known for cardiovascular disease, but later several research investigated its pleiotropic effect that will treat other conditions, such as inflammation, and dermatological conditions, such as psoriasis, acne, and wound healing. Despite that, Rosuvastatin calcium has poor solubility and high permeability in BCS class II; our objective was to incorporate Rosuvastatin calcium into chitosan nanoparticle optimized using DoE and then formulate a topical Carbopol 934 hydrogel loaded with an optimized batch of the nanoparticle. Response surface central composite design was applied to observe the effect of the independent variable on the characteristic of nanoparticles using Design-Expert software, wherein the independent variables are chitosan (X1), sodium tripolyphosphate concentration (X2), and surfactant Tween 80 (X3). On the other hand, dependent responses were entrapment efficiency (Y1), particle size (Y2), zeta potential (Y3), and drug release (Y4). The prepared nanoparticles were spherical and uniform in size. FTIR spectra of drug and excipients reflect no interference between the drug and polymer. The dissolution profile shows the highest 67.48% release after 8 h, and release kinetic analysis confirms that the drug release follows a zero-order sustained release pattern. Furthermore, using a Brookfield viscometer, the prepared hydrogel exhibits good spreadability with a viscosity of 17,065 centipoises. In vitro, 3T3L1 cell line study for viable cells demonstrates that prepared nanoparticles showed the highest viability compared to pure drug and chitosan nanoparticles. The IC50 value for the optimized NP is 123.33 µg/ml, and it shows effective growth of cell closure of scratch after 48 h. The novelty of this present investigation is to evaluate the wound healing activity of Rosuvastatin-loaded chitosan nanoparticles incorporated in carbopol hydrogels by a drug repurposing approach.