Abstract Background Family-based treatment (FBT) is currently the most effective evidence-based treatment approach for adolescents with anorexia nervosa (AN). Home treatment (HT) as an add-on to FBT (FBT-HT) has been shown to be acceptable, feasible and effective. The described three-arm randomized clinical trial (RCT) is intended to investigate whether FBT-HT demonstrates higher efficacy compared to standard outpatient FBT with supplemental mindfulness-based stress reduction training (FBT-MBSR). Methods This RCT compares FBT-HT to standard outpatient FBT and FBT-MBSR as a credible home-based control group in terms of efficacy and delivery. Adolescents with AN or atypical AN disorder (n = 90) and their parent(s)/caregiver(s) are to be randomly assigned to either FBT, FBT-HT or FBT-MBSR groups. Eating disorder diagnosis and symptomatology are to be assessed by eating disorder professionals using standardized questionnaires and diagnostic instruments (Eating Disorder Examination, Eating Disorder Inventory, Body Mass Index). In addition, parents and caregivers independently provide information on eating behavior, intrafamily communication, stress experience and weight. The therapeutic process of the three treatments is to be measured and assessed among both participants and care providers. The feasibility, acceptability and appropriateness can thus also be evaluated. Discussion We hypothesize that FBT-HT will be an acceptable, appropriate and feasible intervention and, importantly, will outperform both established FBT and FBT-MBSR in improving adolescent weight and negative eating habits. Secondary outcome measures include the reduction in the stress experienced by caregivers, as well as the regulation of perceived expressed emotions within the family, while the intrafamily relationships are hypothesized to mediate/moderate the effectiveness of FBT. The proposed study has the potential to enhance the scientific and clinical understanding of the efficacy of FBT for AN, including whether the addition of HT to FBT versus another home-based adjunct intervention improves treatment outcomes. Furthermore, the study aligns with public health priorities to optimize the outcomes of evidence-based treatments and integrate the community setting. Trial registration This study is registered at ClinicalTrials.gov (NCT05418075).