Solid lipid nanoparticles (SLNs) and nanosuspensions (NSs) have shown great promise for improving bioavailability of poorly water-soluble drugs. This study was aimed to develop SLNs and NS of Saquinavir (SQ) for improvement in bioavailability. These formulations were characterized and their pharmacokinetics and biodistribution in mice were evaluated. Saquinavir-loaded SLNs (SQSLNs) showed particle size 215 ± 9 nm and entrapment efficiency 79.24 ± 1.53%, while solid-state studies (differential scanning calorimetry and X-ray diffraction) indicated entrapment of the drug in SLNs. Saquinavir NS (SNS) showed particle size 344 ± 16 nm with fourfold increase in saturation solubility and its solid-state studies showed reduction in crystallinity. Pharmacokinetics and biodistribution studies of orally administered SQSLN and SNS in mice exhibited higher plasma level concentration compared to saquinavir microsuspension (SMS). The relative bioavailabilities for SNS and SQSLN were 37.39% and 66.53%, respectively, compared to 18.87% bioavailability obtained after administration of SMS, indicating suitability of nanoparticulate formulations for improving bioavailability.