ABSTRACT Coloading and codelivery of hydrophilic and hydrophobic drugs as techniques for effective therapy have drawn attention but still present a challenge owing to the opposite nature of both drugs. Therefore, determining a convenient method for coloading and coreleasing hydrophilic and hydrophobic drugs in the development of biomedical devices is important. We constructed multilayer films with a microporous structure for the successful coloading of hydrophilic and hydrophobic drugs. The multilayer films were fabricated using chitosan (CS) and polyacrylic acid (PAA) via layer-by-layer self-assembly. A quartz crystal microbalance (QCM) was used to investigate the self-assembly of (CS/PAA) in films. With a low pH to change the inner structure of the multilayer films, these microporous structures exhibit humidity responsiveness and can return to the original compact structures by treatment with 100% relative humidity. The microporous films can simultaneously load a large number of hydrophobic drugs (tetracycline) and hydrophilic model drugs (Rhodamine B) by wicking and subsequent micropore self-healing. The loading and release ratio of the two drugs in the microporous films is consistent with the initial loading ratio in the solution, providing a good platform for coloading and codelivery of hydrophobic and hydrophilic drugs in biomedical applications.