Oleocanthal and oleacein are olive oil phenolic compounds with well known anti-inflammatory and anti-oxidant properties. The main evidence, however, is provided by experimental studies. Few human clinical trials have examined the health benefits of olive oils rich in these polyphenols. Our aim was to assess the health properties of rich oleocanthal and oleacein extra virgin olive oil (EVOO), compared to those of common olive oil (OO), in people with prediabetes and obesity. This was a randomised, double-blind, crossover trial done in people aged 40-65 years with obesity (BMI 30-40 kg/m2) and prediabetes (HbA1c 5.7-6.4%). The intervention consisted in substituting for 1 month the oil used for food, both raw and cooked, by EVOO or OO. No hypocaloric diet or changes in physical activity were recommended. The primary outcome was the inflammatory status. Secondary outcomes were the oxidative status, body weight, metabolic status and lipid profile. An ANCOVA model adjusted for age, sex and treatment administration sequence was used for the statistical analysis. 91 patients were enrolled (33 men and 58 women) and finished the trial. A decrease in interferon-γ was observed after EVOO treatment, reaching inter-treatment differences (P=0.041). Total antioxidant status increased and lipid and organic hydroperoxides decreased after EVOO treatment, the changes reaching significance compared to OO treatment (P<0.05). Decreases in weight, BMI and blood glucose (p<0.05) were found after treatment with EVOO and not with OO. In conclusion, treatment with EVOO rich in oleocanthal and oleacein differentially improved oxidative and inflammatory status in people with obesity and prediabetes