Ischemic stroke (IS) continues to be a major public health concern and is characterized by significantly high mortality and disabling rates. Inhibiting nerve cells death and enhancing the repair of ischemic tissue are important treatment concepts for IS. Currently, the mainstream treatment strategies mainly focus on short-term care, which underscores the urgent need for novel therapeutic strategies for long-term care. Emerging data reveal that flavonoids have surfaced as promising candidates for IS patients' long-term care. Flavonoids can alleviate neuroinflammation and anti-apoptosis due to their characteristic pharmacological mechanisms. Clinical evidence suggests that long-term flavonoids intake improves IS patients' long-term outcomes. Though the effect of flavonoids in IS treatment has been explored for decades, the neuroprotective pharmacodynamics have not been well established. Thereby, the aim of current review is to summarize the pathways involved in neuroprotective effect of flavonoids. This review will also advance the potential of flavonoids as a viable clinical candidate for the treatment of IS.