IntroductionAndrogen deprivation therapy (ADT) and radiotherapy (RT) increase survival in selected patients with prostate cancer. Nevertheless, the side effects of these therapies are associated with an increased risk of accidental falls and fractures and a decreased quality of life. Preliminary evidence suggests that physical exercise can be a valid strategy to reduce the side effects of ADT and RT in men with prostate cancer. Despite this knowledge, most patients with prostate cancer are insufficiently active, and there is a lack of data on the safety and adherence to the recommended dose of physical exercise. This study protocol is designed to examine the feasibility and safety of a multicomponent experimental physical exercise intervention targeting psychophysical and cognitive functions and the quality of life in this population.Methods and analysisThis is a pilot feasibility study. Twenty-five men currently treated with ADT and RT for prostate cancer will be invited to participate in a 20-week, multicomponent physical exercise intervention, including supervised and unsupervised exercise sessions and meeting the current recommendation for exercise in cancer. The primary outcomes are physical exercise feasibility (recruitment, adherence and drop-out rates) and safety (adverse events related and unrelated to the intervention). The secondary outcomes are muscle strength, balance, fatigue, symptoms of anxiety and depression, cognitive function, quality of life, and patient satisfaction. We will also record the number of accidental falls and fractures occurring during the intervention and at 1 year of follow-up.Ethics and disseminationThe study has received ethics approval from The Area Vasta Nord Local Ethics Committee (Province of Reggio Emilia, 23 June 2020, Number 520/2020/SPER/IRCCSRE). Recruitment began in September 2020 and will be completed in September 2021. The results will be disseminated through scientific journals and conference presentations.Trial registration numberNCT04500080.