Background: Type 2 diabetes mellitus with hyperlipidemia is a common disease. Conventional anti-hyperglycemic and anti-hyperlipidemic drugs have limited efficacies and important side effects, so that alternative agents are needed. Previous studies suggest that fiber-free artichoke (Cynara scolymus L.) leaf extract may have anti-hyperglycemic and anti-hypercholesterolemic effects in hypercholesterolemic type 2 diabetic patients. Moreover, artichoke leaves are used traditionally as an anti-hyperglycemic and anti-hyperlipidemic remedy to treat diabetes mellitus and hyperlipidemia. Objective: The effects of artichoke leaf extract in treatment of hypercholesterolemic type 2 diabetic patients were studied. Methods: In this randomized double-blind placebo-controlled clinical trial with hypercholesterolemic type 2 diabetic patients aged 40 to 60 years not using other anti-hyperlipidemic agents and resistant to daily intake of two 5 mg glyburide tablets and two 500 mg metformin tablets, the efficacy and safety of taking fiber-free artichoke leaf extract (one 400 mg capsule t.i.d. for 2 months) combined with the aforementioned drugs in treatment of 36 patients were evaluated and compared with the placebo group (n = 36). Results: The extract lowered the blood levels of total cholesterol and LDL cholesterol significantly (P=0.002 and p=0.040 respectively) without any significant effects on the blood levels of fasting glucose, postprandial glucose, glycosylated hemoglobin, other lipids, SGOT, SGPT and creatinine (P>0.05) compared with placebo at the endpoint. No adverse effects were reported. Conclusion: Fiber-free artichoke extract may be a safe anti-hypercholesterolemic agent but does not improve glycemic control in hypercholesterolemic type 2 diabetic patients, suggesting the involvement of fibers in the anti-hyperglycemic effect of artichoke.