This study investigates the potential of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) to improve the bioavailability of poorly water-soluble drugs compared to conventional SNEDDS. Conventional SNEDDS contained simvastatin (SIM) at 75% of the equilibrium solubility (S (eq)). Super-SNEDDS containing SIM at 150 and 200% of S (eq) were produced by subjecting the SNEDDS preconcentrates to a heating and cooling cycle. The super-SNEDDS were physically stable over 10 months. During in vitro lipolysis of SNEDDS and super-SNEDDS the SIM concentration in the aqueous phase increased for the first 30 min almost proportional to the drug loads and amounts of preconcentrate employed. The 200% drug-loaded super-SNEDDS generated an amorphous SIM precipitate at the end of in vitro lipolysis. In vivo, the relative bioavailability of SIM from super-SEDDDS increased significantly to 180¿±¿53.3% (p¿=¿0.014) compared to the dosing of two capsules of (dose equivalent) 75% drug-loaded SNEDDS. A significant increase in the terminal half-life of elimination was observed for super-SNEDDS (2.3¿±¿0.6 h) compared to conventional SNEDDS (1.4¿±¿0.3 h) as well as a decreased area under the curve ratio of the SIM metabolite simvastatin acid to the parent compound (0.57¿±¿0.20 and 0.90¿±¿0.3), possibly due to a combination of saturation effects on presystemic metabolising enzymes and prolonged absorption along the small intestine. In summary, this study demonstrated that super-SNEDDS are a viable formulation option to enhance the bioavailability of poorly water-soluble drugs such as simvastatin while reducing the pill burden by an increased drug load of SNEDDS.