AbstractFennel seeds and flaxseed have been traditionally used against many medical ailments due to their medicinal characteristics. The aim of the study was to investigate the health properties of secoisolariciresinol diglucoside (SDG) and anethole from flaxseed and fennel seeds in rats fed with high‐fat diet. Histopathological changes in the heart and liver were also examined. Sixty rats were divided into two main groups. Group I (10 rats) was used as a negative control group and fed on the basal diet only. Group II (50 rats) was fed a hypercholesterolemic diet but not given any drugs during the trial for 2 weeks. This group was further divided into five subgroups (10 rats each). One of them was fed on the basal diet and used as a positive control group. However, the other four subgroups were fed on basal diets and anethole (20 mg/kg/day, orally), SDG (20 mg/kg/day, orally), a mixture of anethole + SDG (10 + 10 mg/kg/day, orally), and atorvastatin (10 mg/kg/day, orally) for 6 weeks. Compared to control, treatment with a combination of anethole + SDG showed a significant (p≤ .05) improvement in serum levels of triglyceride (TG) (137.88 ± 1.61 mg/dL), total cholesterol‐(TC) (180.12 ± 8.99 mg/dL), LDL‐C (46.40 ± 6.67 mg/dL), VLDL‐C (11.81 ± 1.07 mg/dL), aspartate aminotransferase (AST) (75.97 ± 6.92 U/L), alanine aminotransferase (ALT) (34.83 ± 2.17 U/L), alkaline phosphatase (ALP) (130.65 ± 1.05 U/L), and malondialdehyde (MDA) (30.12 ± 1.89 mmol/g), and improved activities of catalase (70.99 ± 3.29 U/g) and superoxide dismutase (SOD) (35.13 ± 2.53 U/dL) enzymes while SDG and anethole group had relatively less impact. Atorvastatin also improved serum levels of triglyceride, total cholesterol, LDL‐C, and VLDL‐C significantly and rose serum high‐density lipoprotein cholesterol (HDL‐C) levels considerably meanwhile it had a minor but negative impact on AST, ALT, and ALP, and negligible impact on activities of MDA, CAT, and SOD enzymes compared to the positive control group. The study revealed that combining anethole and SDG may improve dyslipidemia, improve lipid profile, decrease risks of chronic heart diseases, increase HDL‐C, and enhance antioxidant enzymes' activities.