The main aim of the present study is to improve the dissolution rate of Raloxifene Hydrochloride by formulating nanostructured lipid carriers (NLC) using Quality by Design (QbD) approach. The formulations of NLC-RH were prepared by the ultrasonication method using stearic acid as solid lipid, medium-chain triglyceride as the liquid lipid and polysorbate 80 as the surface-active agent. Two most critical quality attributes (CQAs) for NLC-RH were particle size and entrapment efficiency. The other attributes of medium influence identified includes dissolution rate, zeta potential and particle size didtribution. The Critical Material Attributes (CMAs) identified were solid lipid/liquid lipid ratio and surfactant concentration. The time required for ultrasonication was selected as a Critical Process Parameter (CPP). The 23 full factorial design was used to evaluate the relationship between the CMAs and CPPs variable. Based on the experiments, the composition of the optimal formulation is achieved with solid lipid/liquid lipid ratio of 7:3 and 7 % of surfactant concentration with 15 min of ultrasonication time. The optimized formulation of NLC-RH was found to be with a mean particle size of 146 nm with narrow particle size distributions. From the above results, it is concluded that a promising Raloxifene HCl loaded NLC could give a novel and potential therapy for osteoporosis.