Hyperlipidemia is one of the major risk factors for the development of cardiovascular disease. Many bioactive compounds extracted from plants, particularly polyphenols, have demonstrated a beneficial effect on health. Obtaining these molecules requires extraction, conventional extraction techniques uses solvents whose residue affects these compounds, the environment and the health of consumers. Faced with these problems some techniques, a new axis has been developed it is the dry extraction (controlled sieving-differential spray). Diospyros mesiliformis is poorly studied regarding the bioactive compounds of its fruits. The aim of this study is to find out the optimal conditions for the dry extraction of bioactive compounds compare to solvent extraction and to study antihyperlipidemic activity of the fruit. Granulometric classes ranging from 50 μm to 315 μm were studied. Hydroethanolic and ethanolic extracts of Diospiros mesiliformis were analyzed for total phenolic, total flavonoid, and total tannin contents. For study of antihyperlipidemiac activity, hyperlipidemia was induced by feeding animals with high fat diet daily and orally ad libitum. Ten groups of five animals in each received normal saline, high fat diet, high fat diet plus D. mesiliformis powder (600 mg/kg) and extracts (600 mg/kg) body weight was given in both models and Atorvastatin (10mg/kg) body weight was given in both models respectively for 30 days. At the end of the study, total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL), atherogenic index (AI) of rats were evaluated and were compared with the rats treated with Atorvastatin (10mg/kg) body weight. The particle size and the extracts had high influence on the total phenolic compounds, total flavonoid and tannin content as well as on the antihyperlipidemic activity. Diospyros mespiliformis can be safely used in the treatment of mild to moderate cases of hyperlipidemia considering its easy availability, cost effectiveness, and other beneficial effects.