BACKGROUND: The incidence and prevalence of type 2 diabetes (T2DM) are expected to continue rising. T2DM causes life-threatening, disabling and costly complications, and significantly reduces quality of life and life expectancy. The burden of T2DM can be reduced using comprehensive lifestyle modifications. The aim of this study is to evaluate the applicability and cost-effectiveness of a multicomponent, multidisciplinary lifestyle program in 22 European regions and to generate guidelines for transfer to European health care systems. METHODS: A quasi-experimental study (without a control group) will be conducted to evaluate the CARE4DIABETES program, which is based on the Reverse Diabetes 2Now best practice. The program will involve more than 120 healthcare professionals and 860 people with T2DM from 12 European countries - Belgium, Bulgaria, Finland, Hungary, Italy, Greece, Malta, Poland, Portugal, Slovakia, Slovenia and Spain. Patients will be enrolled based on clinical criteria and motivation for change. The program will have two phases, an intensive phase (6 months) with face-to-face and online training to achieve behavioral change, and an online aftercare phase (6 months) to consolidate changes. The program will be evaluated for impact, sustainability and cost-effectiveness using a combination of validated questionnaires at baseline, six months and one year after the start of the intervention. CLINICAL TRIAL NUMBER: Trial registration number: ISRCTN62063346.