Platinum-ruthenium (PtRu)-based materials are considered the “holy grail” of electrocatalysts for methanol oxidation reaction (MOR) in the fuel cells technique. However, to the best of our knowledge, the exhaustive review report on the advance of PtRu materials for methanol oxidation is rarely summarized for the recent novel achievements. Herein, we summarize and discuss the latest progress of PtRu-based catalysts in MOR. The reaction mechanism of MOR is firstly introduced, and the promotion mechanism is revealed by the relevant activity descriptor, the in-situ spectroscopic analysis and the theoretical calculation. Subsequently, some advanced regulation strategies of PtRu-based catalysts are concluded, including support engineering, morphology design and surface interface regulation. Finally, the challenges and opportunities to improve the MOR performance of PtRu-based electrocatalysts are prospected to further promote the widespread application of PtRu-based catalysts in electrocatalytic systems. It is concluded that many efforts are still required to decipher the atomic scale structure-activity relationship and the structural changes of atoms and electrons in the reaction process by advanced strategies and characterization methods. Hopefully, this review can be helpful for novel PtRu-based catalyst development and understanding their correlation to the structure and performance of energy-relevant electrocatalysis.