［］The long-term efficacy of ischemic stroke (IS) has been constrained by the narrow therapeutic time window, cerebral ischemia-reperfusion injury (CIRI), and the lack of effective neuroprotective agents. Hypoxia-inducible factor-1α (HIF-1α), as a core transcription factor integrating the hypoxic response, regulates key pathological processes such as neuroinflammation, energy metabolism, ferroptosis, autophagy, and angiogenesis, forming a dynamic regulatory network that spans the entire course of IS. This offers a novel target for addressing the aforementioned challenges. This article systematically reviews the research progress over the past three years on traditional Chinese medicine (TCM) interventions in IS through the regulation of the HIF-1α pathway. The results indicate that TCM and its compound formulations can precisely modulate this network in a multi-target, temporally specific, and bidirectional manner, thereby providing comprehensive protection throughout the entire course of IS—from early injury suppression to late-stage repair and promotion. This opens up a unique perspective for the prevention and treatment of IS.