Purpose Recently, there was an increasing interest on the use of ancient grains because of their better health-related composition. The aim of this study was to evaluate in healthy human subjects the antioxidative and diabetes-preventive properties of ancient KAMUT ® khorasan wheat compared to modern wheat. Methods The study was a randomized, non-blind, parallel arm study where the biochemical parameters of volunteers with a diet based on organic whole grain KAMUT ® khorasan products, as the only source of cereal products were compared to a similar replacement diet based on organic whole grain modern durum wheat products. A total of 30 healthy volunteers were recruited and the intervention period lasted 16 weeks. Blood analyses were performed before and after the diet intervention. The effect of KAMUT ® khorasan products on biochemical parameters was analyzed by multiple quantile regression adjusted for age, sex, physical activity and BMI compared to data at baseline. Results Subjects receiving KAMUT ® khorasan products showed a significantly greater decrease of fat mass ( b  = 3.7%; CI 1.6–5.5; p  = 0.042), insulin ( b  = 2.4 µU/ml; CI 0.2–4.2; p  = 0.036) and a significant increase of DHA ( b  = − 0.52%; CI − 1.1 to − 0.12; p  = 0.021). Conclusions Our study provides evidence that a substitution diet with KAMUT ® khorasan wheat products can reduce some markers associated to the development of type-2 diabetes compared to a diet of modern wheat.