Microparticles made from naturally occurring biopolymers, such as chitosan, appear to be promising carrier systems for the sustained release of orally administered drugs. In the current study, we followed a microencapsulation technique based on the spray-drying method to prepare metoprolol tartrate-containing chitosan microparticles with various compositions. The prepared microparticulate drug delivery systems were investigated for their morphological, structural, and thermal behavior by optical microscopy, infrared spectroscopy, and thermogravimetric analysis. Microencapsulation efficiency and drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastric fluid (SGF) (pH 1.2) and simulated intestinal fluid (SIF) (pH 6.8) revealed that the drug-to-polymer ratio is an important element in controlling the release features of microparticulate systems based on CHT. Also, the pH of the dissolution fluid plays an important role in the release of the drug substance from the microspheres. Additionally, the analysis of the release kinetic mechanism concluded that in SGF media as well as in SIF media, the MT from the chitosan-based microparticles is released by means of a Fickian diffusion process.