Due to the limited effects of current treatments on brain repair and regeneration, stroke continues to be the predominant cause of death and long-term disability on a global scale. In recent years, hydrogel-based biomaterials combined with stem cells and extracellular vesicles have emerged as promising new treatments to improve brain regeneration after stroke. However, the clinical translation of hydrogel-based biomaterials for the treatment of brain injury is still far from satisfactory. In this review, we first summarise the present status of stroke-related clinical treatments and the advantages provided by hydrogel-based materials in combination with stem cells and extracellular vesicles in preclinical studies. We then focus on the possible causes of the gap between preclinical studies and clinical translation of hydrogel-based biomaterials from the perspective of biocompatibility and safety, the choices of preclinical models, the lack of clinical noninvasive imaging methods, standardisation and quality control, manufacturing scalability, and regulatory compliance. With the progress in the abovementioned areas, we believe that the clinical translation of hydrogel-based biomaterials will greatly improve brain regeneration after stroke and that this improvement will be realised by the general public in the near future.