This article presents the development of lyophilized orally disintegrating tablets prepared with the dry emulsion technique to enhance the in-vitro dissolution and in-vivo performance of the poorly bioavailable drug atorvastatin calcium (ATV). Tablets were fabricated by freeze-drying o/w emulsions of ATV. The Emulsions were prepared using a matrix former solution (alginate or gelatin, 2 or 4%) containing a sugar alcohol (mannitol) and a collapse protectant (glycine) as the water phase and Labrafac® as the oil phase in the presence of surfactant (synperonic® PE/P 84 or synperonic® F108) under proper homogenization. The influence of formulation parameters on friability of the prepared tablets, disintegration time and in-vitro dissolution of the drug from these tablets were investigated. Results showed the significant influence of the matrix former and emulsifier type on the disintegration time. In-vitro dissolution study revealed the enhanced dissolution rate of ATV from the lyophilized dry emulsion tablets (LDET) compared to the plain drug. DSC and XRD studies of the optimized ATV-loaded LDET proved the presence of the drug in the amorphous form. SEM images showed the intact, porous and non-collapsible structure of the prepared LDET with complete loss of ATV crystallinity. Administration of ATV-loaded LDET to high fat diet-induced hyperlipidemic rats demonstrated a significant decrease (p < 0.05) in the serum and tissue levels of the tested parameters compared to the market product used. The obtained results suggest a promising, easy-to-manufacture and effective dosage form for the treatment of hyperlipidemia.