Propane dehydrogenation (PDH) technology has been considered an important breakthrough to cope with the ever-increasing demand for propylene. Developing high-performance non-noble metal catalysts has emerged as an effective approach for replacing the currently used commercial Pt- and Cr-based catalysts with high cost and toxicity. Metal oxides have attracted much attention as PDH catalysts due to their high C-H activity, abundant active sites, and desirable dehydrogenation pathways. Regulating the supports and active sites through the rational design of structure and composition provides a new promising platform to improve the dehydrogenation activity and stability of metal oxide catalysts. This review systematically summarizes the catalytic mechanism of PDH. The rational design of metal oxide catalysts with suitable supports and precisely modulated active sites is described with their catalytic performances. In addition, the important roles played by reaction conditions to promote PDH processes are discussed. Furthermore, combined with well-developed advanced characterization methods, the in-depth exploration of the metal oxide-based PDH catalysts is highlighted. Finally, some perspectives for metal oxide-based PDH catalysts are concisely proposed to achieve their future innovations and industrialization.