The goal of the present study was to formulate and evaluate a topical gel of nanoparticulate andrographolide for the anti-bacterial and inflammation effect that would attenuate the first-pass metabolism following oral administration. Nanoparticulate andrographolide was fabricated by the solvent evaporation method and optimized using size, polydispersity index, and physical stability properties. The dispersion was converted into a dermal gel using three gelling agents. The optimal gel formulation based on Carbopol 934 at 0.25% concentration showed four-fold higher drug release through a mouse skin model and 26-fold higher drug retention in the skin compared to the gel formulation containing saturated suspension. The anti-inflammation activity of andrographolide suggests also that the topical gel as a promising dosage form for dermal delivery of poorly water-soluble and extensively metabolized andrographolide.