Abstract <p>Therapeutic strategies targeting mitochondria, which is at the centre of cellular energy metabolism and a significant source of reactive oxygen species, have become a particular focus in research. Advances in nanomedicine have provided new approaches for mitochondria-targeted therapies, mainly including lipophilic cations and mitochondria-targeted peptides. However, in cerebral ischaemia–reperfusion injury (CIRI), targeted treatment is more complex due to the presence of the blood–brain barrier. This topic has emerged as a critical area of research. This review introduces the common strategies of mitochondrial targeting, focuses on the targeting role and overall efficacy of mitochondria-targeted nanoparticles in CIRI models and finally analyses the advantages and potential shortcomings of this therapeutic strategy in CIRI. This article provides a valuable theoretical basis and useful research ideas for the further development and optimisation of mitochondria-targeted nanotherapeutic strategies for CIRI.</p> Graphical Abstract <p></p>