Aims: The aim of the present study is to formulate and evaluate the Salvia miltorrhizaloaded Nano-structured lipid carriers(SM-NLC) in order to enhance the aqueous solubility and bioavailability as the efficacy of Salvia miltiorriza extract has been restricted due to less solubility and low bioavailability. Introduction: Salvia miltiorrhiza is a well-known Chinese herb that belongs to the family Labiatae. The herb has been widely used to treat various kinds of ailments, and its main phytochemical constituents are Tanshinone I, Tanshinone II, Miltirone, and Salvionolic acid, which are mainly found in the extract of roots. These Phytochemical constituents are responsible for several pharmacological activities such as anti-oxidant, anti-microbial, anti-hyperlipidemic, anti-inflammatory, cardiovascular diseases etc. Objective: Nano-lipid carriers are useful in enhancing the solubility of poor water-soluble drugs. The faulty lattice arrangement of Nano-lipid carriers (NLC) provides better entrapment, thus providing more space for the drug to incorporate in the lattice structure of NLC, improving the stability of the formulation and preventing the drug leakage from the matrix. Methods: SM-NLCs were prepared by using oleic acid and stearic acid as liquid and solid lipids, respectively and tween 80 as the surfactant by high-speed homogenization method. The optimization of SM- NLC was performed by applying the Box-Behnken experimental design. The independent variables were chosen as the amount of lipids, surfactant concentration, and sonication time, whereas dependent variables were opted as particle size and entrapment efficiency. The influence of different proportions of the lipids (Stearic acid and Oleic acid) and the surfactant (Tween 80) was analysed on the dependent variables. The optimized formulation was evaluated for Particle size (241.7nm±3), Polydispersity index (.249 ±0.05), Zeta Potential (-14.6±5), and entrapment efficiency (82.49%). Scanning Electron Microscopy (SEM) was performed to identify the surface morphology, and the entrapment of the drug into the nanostructured matrix was verified by Differential Scanning Calorimetry. The interaction between the formulations was confirmed by performing FTIR. The dialysis bag method was performed to calculate the in vitro drug release from the optimized formulation. Additionally, a stability study was performed for 1 month of duration. Result: The SM NLCs were successfully formulated based on the Box-Behnken design. Particle size, PDI, zeta potential, and EE demonstrated less than a 5% difference compared to the predicted value. The formulations did not show any possible interactions with the lipids. The optimized formulations were found stable after one month of stability studies. Conclusion: The above results confirmed that Salvia miltiorrhiza could be effectively formulated in the form of a nanostructured-lipid carrier system. The formulation and evaluation of nanoparticles have been performed successfully using the homogenization method.