In this study, Gambogenic acid loaded by solid lipid nanoparticles (GNA-SLNs) was explored to reduce toxicity and improve therapeutic efficacy. GNA-SLNs were prepared by emulsification and low temperature solidification methods, and the freeze-dried powders were then developed to improve the stability. The physical-chemical properties of the products in terms of particle size, zeta potential, morphology and entrapment efficiency were well evaluated. The results revealed that the mean diameter, polydispersivity index (PI), zeta potential, and the entrapment efficiency of the nanoparticles were 163.3 nm, 0.203, -16.9 mV and 61.2%, respectively. In comparion with GNA-SLNs, the freeze-dried solid lipid nanoparticles (SLNs) showed a slight augmentation in the mean particle size (from 163.3 to 173 nm) and PI (from 0.203 to 0.253), and no significant modification in the zeta potential, entrapment efficiency and drug loading. In vitro release kinetics based on a dialysis method demonstrated that Gambogenic acid (GNA) was released in a prolonged fashion for 96 h and followed Higuchi equation unitarily. The release profile did not show any significant modification after the freeze-drying process. The Pharmacokinetic study was carried out, the i.p. administration of GNA formulations to rats at doses of 2.5mg/kg. AUC((0-t)) was increased (up to 3.1-fold) and clearance was decreased (up to 3.03-fold) when GNA entrapped in SLNs. In conclusions, the freeze-dried powders form could enhance the long-term stability of SLN, and solid lipid nanoparticles encapsulation could effectively strategy to change the poor aqueous solubility and prolong the half-life of GNA.