The present research work deals with fabrication of indomethacin loaded gelatin nanoparticles prepared by double desolvation method for controlled drug delivery. Submicron polymeric particles with size in-vitro drug release profile showed initial burst release (>20% in 1 hr) followed by controlled release (>75% in 12 hr). Among the kinetic models employed, the Higuchi model showed a better fit (R 2 > 0.9) with n P ≤ 0.001) decreased the paw volume as compared to IDM. Pharmacokinetic study showed significant enhancement (P t max value was 3 h for IGNP compared to 1 h for IDM. C max of IGNP had higher value (110.81 ± 8.53 g/mL) compared to that of IDM (51.66 ± 7.5 g/mL). AUC0–12 was 1009.78 ± 80.24 and 194.33 ± 46.76 μg·h/mL in IGNP and IDM respectively (relative bioavailability 500%). Further, a good in vitro-in vivo correlation established the formulation for future trials.