Background: Osteoarthritis treatment generally involves using a Non-steroidal Anti-inflammatory Drug (NSAID), and the most common is Diclofenac sodium. The oral use of diclofenac sodium presents some adverse effects on the gastrointestinal tract. Trans-dermal diclofenac sodium's biological efficacy can be affected by factors including its log P value of 1.13. Nanostructured Lipid Carrier (NLC) may solve these concerns. Objective: This study examined how stearic and oleic acid concentrations customise diclofenac sodium NLC's physicochemical properties. Method: High shear homogenisation was used to compare stearic acid and oleic acid at 6:4, 7:3, and 8:2. Furthermore, the physicochemical properties of diclofenac sodium NLC were assessed, such as organoleptic, particle size and poly-dispersity index, pH, viscosity, zeta potential, entrapment efficiency, profiles of FTIR and DSC. Result: This study found that particle size ranged from 333.60 ± 144.29 to 791.77 ± 85.57, and entrapment efficiency was 89.38 ± 3.69 to 76.96 ± 3.29. Increasing the content of oleic acid as a liquid lipid reduces particle size and improves diclofenac sodium NLC entrapment. According to One-Way ANOVA, the dependent variable was not significantly affected by any independent variables (p-value > 0.05) except for particle size and entrapment efficiency. Conclusion: Stearic acid-oleic acid concentration ratios affect diclofenac sodium NLC's physicochemical properties.