The objective of current study was to develop solid lipid nanoparticles-loaded with simvastatin (SIM-SLNs) and investigate their in vivo anti-hyperlipidemic activity in poloxamer-induced hyperlipidemia model. Nano-template engineering technique was used to prepare SIM-SLNs with palmityl alcohol as lipid core and a mixture of Tween 40/Span 40/Myrj 52 to stabilize the core. The prepared SIM-SLNs were evaluated for physicochemical parameters including particle diameter, surface charge, morphology, incorporation efficiency, thermal behaviour and crystallinity. In vitro release profile of SIM-SLNs in simulated gastric and intestinal fluids was evaluated by using dialysis bag technique and anti-hyperlipidemic activity was assessed in hyperlipidemia rat model. SIM-SLNs revealed uniform particle size with spherical morphology, zeta potential of −24.9 mV and high incorporation efficiency (∼85%). Thermal behaviour and crystallinity studies demonstrated successful incorporation of SIM in the lipid core and its conversion to amorphous form. SIM-SLNs demonstrated a sustained SIM release from the lipid core of nanoparticles. SIM-SLNs significantly reduced the elevated serum lipids as indicated by ∼3.9 and ∼1.5-times decreased total cholesterol compared to those of untreated control and SIM dispersion treated hyperlipidemic rats. In conclusion, SIM-SLNs showed a great promise for improving the therapeutic outcomes of SIM via its effective oral delivery.