BackgroundExtensive evidence has suggested the cardio-protective properties of the polyphenol curcumin. The aim of this study was to investigate the effects of a highly bioavailable curcumin supplement on cardiometabolic risk factors, health-related quality of life, and depression in patients with coronary slow flow phenomenon (CSFP).MethodsThis randomized double-blind placebo-controlled clinical trial was conducted in 42 patients with CSFP (age 35–70 years, 25 ≤ body mass index < 40 kg/m2). Patients received either 80 mg/day nano-curcumin or placebo for 12 weeks. Serum levels of visfatin, high-sensitivity C-reactive protein (hs-CRP), and glycemic indices were measured before and after the intervention. The short form 36-item quality of life (SF-36) and Beck’s Depression Inventory-II (BDI-II) questionnaires were assessed, as well.ResultsNo significant improvements were observed in circulating hs-CRP and visfatin following the intervention. A significant increase was observed in pre- to post-fasting blood glucose (− 0.9 ± 12.2 vs. 7.7 ± 12.4 mg/dl, p = 0.02) and hemoglobin A1C (− 0.1 ± 0.8 vs. 0.5 ± 0.8%, p = 0.04) levels, in the placebo compared with the intervention group. Physical (8.2 ± 8.1 vs. − 1.2 ± 6.5, p < 0.001) and mental (6.8 ± 11.8 vs. − 1.1 ± 10.4, p = 0.02) component summary scores were significantly improved in the nano-curcumin than the placebo group. Additionally, the number of patients with lower degrees of depression was significantly better in the intervention than the placebo group following the supplementation (p = 0.046).ConclusionCurcumin supplementation prevented deterioration of glycemic control and improved physical and psychological quality of life and depression in patients with CSFP.Trial registrationIranian Registry of Clinical Trials (IRCT20131125015536N8), June 19, 2019.