Breast cancer is the most commonly diagnosed cancer and the major cause of cancer-related death among females. Studies on natural compounds used alone or in combination with chemotherapeutic agents proved their efficacy to treat and prevent cancer. Hesperidin, Piperine, and Bee venom displayed anti-oxidant and anti‑cancer activity against various types of cancers and cell lines and can be used in combination with Tamoxifen with the aim to decrease cytotoxicity profile. In-vivo study of Piperine (Pip), Bee venom (BV) and hesperidin (Hes) as a single treatment or in combination with/without tamoxifen indicated low hepato-nephrotoxicity and hepato-nephroprotective against tamoxifen-treated and untreated xenograft MCF-7 induced breast cancer. Serum ALT, AST, ALP activities and creatinine, and urea level were elevated. MDA level was increased with a marked reduction in SOD activity in the untreated xenograft MCF-7 induced breast cancer. Treatments for these natural products improve these parameters. It could be concluded that alone or in combination with/ without Tamoxifen clarified a modulatory role against breast cancer.