In last decades, diet and dietary components have been regarded as important strategies to prevent the development or mitigate numerous chronic diseases, including inflammation, cardiovascular pathologies, cancer, etc. One of the most common dietary components of Asian population is soy. A plethora of research shows the promising effect of soy soy-based foodstuffs and genistein, which is one of the predominant isoflavone compounds, in the prevention and mitigation of stroke. Growing evidence shows that genistein, which is a selective estrogen receptor modulator, mitigates ischemic stroke-induced damages through the modification of oxidative stress and molecular pathways. The promising pharmacological role of genistein is attributed to its ability to suppress nuclear factor (NF)-kappa B and Akt signaling pathway, direct antioxidant action, and targeting estrogen and androgen-mediated molecular pathways which help to mitigate stroke damages and prolong cell survival. In this work, we systematically review the current reports on the therapeutic role of genistein against ischemic stroke and its molecular mechanism of actions.