Electrochemical water splitting has great potential in the storage of intermittent energy from the sun, wind, or other renewable sources for sustainable clean energy applications. However, the anodic oxygen evolution reaction (OER) usually determines the efficiency of practical water electrolysis due to its sluggish four-electron process. Layered double hydroxides (LDHs) have attracted increasing attention as one of the ideal and promising electrocatalysts for water oxidation due to their excellent activity, high stability in basic conditions, as well as their earth-abundant compositions. In this review, we discuss the recent progress on LDH-based OER electrocatalysts in terms of active sites, host-guest engineering, and catalytic performances. Moreover, further developments and challenges in developing promising electrocatalysts based on LDHs are discussed from the viewpoint of molecular design and engineering.