AbstractCurcumin is a phytochemical isolated from the dried rhizome of Curcuma longa L. family Zingiberaceae which possesses versatile biological activities and has hydrophobic properties. The current study was conducted to fabricate, and optimize curcumin loaded chitosan and Sodium tripolyphosphate (STPP) nanoparticles (NPs) to improve the bioavailability of curcumin. NPs were fabricated employing the Ionic gelation method. Four formulations were developed based on the selected variables like STPP and chitosan concentration, rotations per minute (rpm), temperature, and pH of chitosan solution. NPs were characterized for morphology, drug-polymer compatibility, yield, particle size, encapsulation efficiency, release behavior, anti-inflammatory and anti-arthritic activity compared to curcumin and standard drug. Fourier transform infrared spectroscopy (FTIR) shows nanoparticle compatibility. The maximum yield was 60%. Entrapment efficiency ranged from 45 to 65%. Curcumin NPs and standard drug 600 µg/ml shows 59% and 70% anti-inflammatory activity by HRB membrane stabilization method respectively which are greater than curcumin alone whereas anti-arthritic activity by protein denaturation method which is also comparable to standard drug and greater than curcumin was 66 and 70% respectively. Statistical analysis shows the mean significant difference at p ≤ 0.05. The study concluded that curcumin-loaded chitosan and STPP NPs formulated successfully by the Ionic gelation method, which increased curcumin absorption leading to a reduced dosing rate and improved patient compliance.