Objective: The objective of this paper was to fabricate and increase the effectiveness of the formulation of Solid lipid nanoparticle (SLN) on improving the oral bioavailability of Famotidine. Methods: In this study, ultrasonic-hot emulsification technology was used to manufacture Famotidine-SLN. Subsequently, the particle diameter, electrokinetic potential, and Encapsulation Efficiency of SLN were all determined during the characterization process. Results: The results showed that the average particle size of SLN containing Famotidine was prepared on average 151.90 ± 26.05nm and relatively small size distribution (0.35 ± 0.04). Famotidine- SLN had high entrapment efficiency in average 82.30 ± 4.39 %. Famotidine-SLN showed a 3.5-fold increase in Cmax and a 4.3-fold increase in AUC0-∞ than free Famotidine suspension. Conclusions: SLN improved oral bioavailability of Famotidine significantly compared with Famotidine suspension. SLNs seem to offer a potential delivery strategy to increase the solubility and bioavailability and permeable medicines.