The synthesis of Copper Nanoparticles (CuNPs) using Ruku (Ocimum tenuiflorum) leaf extract from Sumbawa-Nusa Tenggara Barat as capping agent has been conducted. The effect of reaction parameters such as copper precursor concentration, leaf extract concentration, and reducing agent concentration was studied. O. Tenuiflorum leaf extract induces the reduction of Cu2+ ions to CuNPs and acting as a capping agent. The formation of CuNPs was monitored using UV-Visible spectrophotometer at different stages during the synthesis process. Box-Behnken Experimental Design with response surface methodology was applied to optimize the synthesis parameters. The results show that the correlation coefficient between UV-Vis absorption response and input variables was 0.99 using second-order equation. Optimization result using RSM-Box-Behnken Design obtained that the optimum synthesizes condition was at 0.12 to 0.14 M CuSO4, 0.20 to 0.24 M Na3C6H5O7 and 2 to 3 mL extract. The copper nanoparticles that synthesized have a spherical shape with an average size of 22.09 nm.