Purpose In this systematic review we included clinical studies from 1800 until 2020 to evaluate evidence of the effectiveness of homeopathy on physical and mental conditions in patients during oncological treatment. Method In February 2021 a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsychInfo, CINAHL and Medline) to find studies concerning use, effectiveness and potential harm of homeopathy in cancer patients. Results From all 1352 search results, 18 studies with 2016 patients were included in this SR. The patients treated with homeopathy were mainly diagnosed with breast cancer. The therapy concepts include single and combination homeopathic remedies (used systemically or as mouth rinses) of various dilutions. Outcomes assessed were the influence on toxicity of cancer treatment (mostly hot flashes and menopausal symptoms), time to drain removal in breast cancer patients after mastectomy, survival, quality of life, global health and subjective well-being, anxiety and depression as well as safety and tolerance. The included studies reported heterogeneous results: some studies described significant differences in quality of life or toxicity of cancer treatment favouring homeopathy, whereas others did not find an effect or reported significant differences to the disadvantage of homeopathy or side effects caused by homeopathy. The majority of the studies have a low methodological quality. Conclusions For homeopathy, there is neither a scientifically based hypothesis of its mode of action nor conclusive evidence from clinical studies in cancer care.