Inspired by the restoration of the superhydrophobic surfaces after the damage in nature such as lotus leaf and clover, smart self-healing coating with controllable release of loaded healing agents is both of scientific and technological interest. Herein, a smart self-healing coating with superhydrophobicity was gained through blending UV/NIR/acid/base multiple-responsive ZnO-encapsulated mesoporous polydopamine (MPDA) microspheres (zinc oxide-encapsulated mesoporous polydopamine microspheres) with silicone latex and hydrophobic nanoparticles. The hydrophobic and micro/nanostructured ZnO-encapsulated MPDA microspheres provided UV/NIR/acid/base multiple response sources for the smart self-healing coating, combining the photocatalytic activity and acid/base solubility of ZnO nanoparticles, zwitterionic characteristic of amino-modified silicone oil (ASO), as well as the photothermal conversion abilities and charge characteristics of PDA. The ZnO nanoparticles simultaneously acted as the protective layer for the stimuli-responsive microspheres and functional filler in the coating, contributing to realize the controllable and long-period release of loaded hydrophobic ASO and the further antibacterial functionalization for the coating. The super/high hydrophobicity and antibiofouling performances of the coating could be self-healed by UV, NIR, acid, or base stimuli, attributing to the release of ASO from the microspheres. Then, largearea, rapid, and controllable healing superiority could be achieved on the coating with the combined multiple responses under different conditions. Robust environmental endurances for superhydrophobic coating were also confirmed under harsh environments by directly exposing to UV-accelerated weathering and immersing into various solutions (including strong acid/base, salt, and artificial seawater solution). This smart coating has high application prospects due to its environmentally friendly nature, excellent self-healing, and multifunctional characteristics, and the multiple-responsive ZnO-encapsulated MPDA microspheres can be used for the functionalization of other materials.