Ulcers are sores or eroded areas that form in the lining of the digestive (gastrointestinal) tract. They usually occur in the stomach (gastric ulcer) or in the duodenum (duodenal ulcer). Proton pump inhibitors (PPIs) are the most potent inhibitors of gastric acid secretion available, and they are effective for treating all acid-related disorders Esomeprazole is indicated for the treatment of gastroesophageal reflux disease in adults and children, risk reduction of NSAIDs-associated gastric ulcer, Helicobacter pylori eradication and control of pathological hypersecretory conditions associated with Zollinger–Ellison syndrome. Nowadays, targeting drug delivery is the major problem which is being faced by the researchers. Target oriented drug administration with improvements in therapeutic efficacy, reduction in side effects and optimized dosing regimen, shall be the leading trends in the area of therapeutics. Nanosponges are a new class of materials and made of microscopic particles with few nanometers wide cavities, in which a large variety of substances can be encapsulated. These particles are capable of carrying both lipophilic and hydrophilic substances and of improving the solubility of poorly water soluble molecules. The aim of this study is to formulate & evaluate nanosponge loaded with Esomeprazole. The nanosponge was prepared by standard methods & evaluated for various parameters. The result showed that the bulk density and the tapped density for all the formulations varied from 0.345 to 0.385gm/cm3 and 0.458 to 0.492gm/cm3 respectively. The result of Hausner’s ratio of all formulations ranges from 1.278 to 1.328. Compressibility index of all the formulations ranges from 21.75% to 24.67%. The kinetics study revealed that formulations was found to follow Zero order of drug release kinetics. The actual drug content of prepared nanosponge’s formulation F1, F2, F3, F4, F5 and F6 was found to be 94.45±0.32, 92.23±0.25, 97.74±0.15, 99.45±0.26, 98.85±0.36 and 92.23±0.14 respectively. The maximum drug content was found in formulation F3 (99.45±0.26). The Encapsulation efficiency of formulation F1, F2, F3, F4, F5, and F6 was found 74.56±0.22, 73.36±0.25, 85.45±0.36, 78.85±0.14, 82.23±0.25 and 81.14±0.35. The maximum encapsulation efficiency was also found maximum in formulation F3 (85.45±0.36). It can be concluded that F3 nanosponge of Esomeprazole can be used for treating gastric ulcer as it exhibits all ideal characteristics. Keywords: Nanosponge, Gastric ulcer, Esomeprazole, Targeted drug delivery