The dataset includes four curcumin-loaded nanoparticle formulations (CO-LLN, MG-LLN, HPO-SLN, and CN-SLN) differing by lipid type. Each formulation was characterized for particle size, ζ-potential, and physical stability. In vivo data were collected from 16 female Sprague Dawley rats divided into four treatment groups, each receiving 250 mg/kg curcumin orally. Biological samples included plasma, gastrointestinal segments, liver, kidney, and adipose tissues. Curcumin and its metabolites were quantified in these samples using LC-ESI–MS/MS. Overall, the dataset integrates formulation parameters, physicochemical properties, and in vivo biodistribution profiles of curcuminoids.