This study aimed to present an effective formulation targeting oral ulcers that will remain in the application site for a longer period, reducing the frequency of administration. As a candidate formulation, usnic acid (UA) was loaded into the optimum nanogels. The characterization studies included physical, rheological, and bioadhesive properties as well as in vitro release and ex vivo studies. The rheological results revealed that the nanogels present pseudoplastic flow behavior. In vitro drug release showed a prolonged pattern. In further, the chosen UA nanogels showed very low percentages of penetration and permeation. F13, which showed the highest release, suitable bioadhesive properties (0.475 +/- 0.033 N/cm(2)) and eligible particle size (250.22 +/- 4.11 nm), PDI (0.089 +/- 0.052), and zeta potential (20.56 +/- 0.330 mV) values were chosen for in vivo experiments. The selected UA nanogels showed effective antimicrobial activity against Bacillus Cereus and great in vivo wound healing properties. The results indicated that suitable UA nanogels with desired properties could be prepared. The therapeutic potential of the nanogels for oral ulcers was assessed using an animal model and the histopathological findings suggested that the optimized formulation is a good choice for oral ulcer treatment. Nonetheless, further research is recommended to support its efficacy by applying pharmacodynamic and pharmacokinetic studies in human individuals.