This study delved on development of curcumin loaded Nanostructured Lipid carrier (NLC) incorporated into gastro-retentive oral in situ gel for specifically designed to the stomach delivery. Curcumin is less soluble in stomach pH, so a high amount of drug would be required to produce the desired effects. The solubility of curcumin was improved by the NLC. The curcumin loaded NLC was fabricated using a high shear homogenization technique. Through lipid screening, Precirol ATO 5 and Labrafac PG were chosen as a lipids, and tween 80 was selected as a surfactant in this formulation. A formulation (NLC-F4) comprising 2% lipids and 800 mg of surfactant was chosen as the best formulation, average mean particle size was found to be 119.3 ± 0.13 nm, PDI was found to be 0.127 -30 ± 0.17 mV 0.02, zeta potential was found to be -30 ± 0.17 mV and % of encapsulation efficiency were found to be83.4 ± 1.5%. FT-IR investigation showed no interactions. Scanning Electron Microscopy (SEM) revealed smooth and spherical shaped particles, while Differential Scanning Calorimetry (DSC) assessment suggested that curcumin was completely distributed in the NLC. The in vitro drug release of curcumin from NLC-F4 showed 8 times enhanced drug release compared with the pure curcumin in pH 1.2 buffer. In vitro antioxidant and anti-inflammatory studies revealed significant effects compared to reference standards. Drug release kinetics followed first order release and Weibull kinetics models. The curcumin loaded NLC was fabricated into anoral in situ gel to enhances the gastric retention time and prolong release of drug in the stomach. The system exhibited quick gelation time, optimal viscosity, gastric buoyant density, 24 hours floating time, gastric peristalsis resistant gel strength, and sustained drug release. These investigations revealed that an oral in situ gelling system containing curcumin loaded NLC has potential as a carrier for stomach specific delivery and could serve as an alternative dosage form compared to conventional ones for treating gastric ulcers in patients.