Background Current guidelines emphasize cancer patients should increase their physical activity levels, encouraging physical exercise practice as a complementary therapy to mitigate adverse effects during treatment. Telehealth can be a feasible method to improve adherence and interventional support for breast cancer patients, of which most do not meet sufficient physical activity levels after diagnosis. The Adaptations to Breast Cancer and Exercise Using Telehealth (ABRACE: Telehealth) study aims to investigate the effects of a 12-week telehealth multicomponent training program plus a health education program (MTHE), compared to a health education program alone (HE), on physical and psychological outcomes in breast cancer patients undergoing treatment. Methods This study is a randomized controlled trial. Women undergoing primary treatment (during or after chemotherapy) for breast cancer (stages I–III) will be randomly assigned to MTHE (twice a week) or HE (once a week). MTHE components are mobility, aerobic, balance, resistance, and flexibility home-based exercises, supervised by video call. The primary study outcome is cancer-related fatigue. The secondary outcomes are quality of life, symptoms of depression and anxiety, physical activity level, cancer-related cognitive impairment, and functional capacity. Other outcomes are adherence to interventions and a follow-up questionnaire evaluating the individual perception in motivation, lifestyle changes, and main barriers to participation. All outcomes will be remotely assessed before and after intervention. Our analysis will follow the intention-to-treat approach and per-protocol criteria, with additional sub-group analysis. Discussion To our knowledge, this is the first randomized clinical trial in breast cancer patients using a face-to-face videoconference strategy to supervise physical exercise. Our hypothesis is of superiority for the effects of MTHE on primary and secondary outcomes compared to the effects of only the health education intervention. Trial registration Adaptations to Breast Cancer and Exercise Using Telehealth (ABRACE: Telehealth), NCT04641377. Registered on 23 November 2021, https://clinicaltrials.gov/ct2/show/NCT04641377