Defect engineering and anionic regulation are effective approaches to improve the intrinsic activity of oxygen evolution reaction (OER) catalysts, particularly for highly efficient and low-cost cobalt-based electrocatalysts. Layered double hydroxides (LDHs) are considered as promising electrocatalysts toward OER. However, their electronic properties and active sites need to be optimized for their large-scale application. Herein, rapidly cationic defect and anion dual-regulated CoAl LDHs (PS-CoAl LDHs) were in situ synthesized in a few minutes via a modified water DBD plasma treatment. Abundant Al3+ vacancies and a relatively rough surface for S2- regulation were formed by the etching effect of the plasma. Consequently, the as-obtained PS-LDHs possess improved intrinsic conductivity and an optimal electronic structure. Simultaneously, the synergistic effect of the Al3+ vacancies and S2- regulation promote the exposure of active Co sites, resulting in an amorphous and porous surface for improving the OER performance.