This study investigated the chemical composition, in vivo antioxidant, and antihyperlipidemic potential of Ajwa date polyphenol extract (DPE). Chemical analysis revealed that the Ajwa dates contain substantial amounts of carbohydrates, energy, potassium, iron, polyphenols, and flavonoids. In vivo studies showed that feeding rats with cholesterol‐rich diets significantly (p ≤ 0.05) increased their body and liver weights, total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), very‐low‐density lipoprotein cholesterol (VLDL‐C), and triglycerides (TG) in plasma and liver, and reduced the high‐density lipoprotein cholesterol (HDL‐C) content and antioxidant enzyme activities. However, oral administration of 25, 50, and 100 mg DPE/kg body weight to hypercholestrolemic rats, significantly (p ≤ 0.05) reduced their body and liver weights, total hepatic cholesterol, LDL‐C, VLDL‐C, and triglycerides. Furthermore, treatment with DPE improved (p ≤ 0.05) the HDL‐C concentration and antioxidant enzyme activity in a concentration‐dependent fashion, thereby regulating lipid profiles, enhancing the antioxidant defense system. Overall, DPE showed significant (p ≤ 0.05) nutritional, antioxidants, and antihyperlipidemic benefits. Practical applications Coronary heart disease is the leading cause of death in the world. Consumption of fruits and vegetables rich in polyphenol have shown to exert cardio‐protective effect. This work revealed that phenolic extracts of Ajwa dates have positive impacts on the health as it reduced TC, LDL‐C, and lipids VLDL‐C and improved HDL‐C and the antioxidant defense system in rats. The findings of this study could aid in the profound understanding of the nutritional and health potentials of Ajwa dates and thus could help in utilization of these valuable fruits for the prevention and curing of cardiovascular diseases.