Inspired by the crucial role of nature hydrophobic regions in highly efficient enzymatic catalysis, this work proposes a simple but valid catalyst-design strategy by simply employing the interlayer region of layered double hydroxides (LDHs) to mimic the bilayer structure of nature phospholipids. The interlayer region of LDHs intercalated with dodecyl sulfonate, an amphiphilic species, provides bidimensional hydrophobic environments for encapsulated Mn(TPP)OAc. The Mn centers encapsulated in the hydrophobic interlayer region of LDHs has been found to exhibit superior catalytic activity to homogeneous counterpart in the epoxidation of a variety of alkenes, including cyclohexene, heptylene, phenylethylene, 3-methyl-3-buten-1-ol, and even functional alkenes such as ethyl cinnamate and chalcone. It has also been found that TOF increases with decreasing polarity of the catalyzed substrate while TON depends on the polarity difference between the catalyzed alkene and produced epoxide.