Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles with tunable diameters and a uniform morphology were constructed in dimethyl sulfoxide (DMSO)/H2O mixed solvents and were further decorated with dextran to improve their stability and biocompatibility. A series of reaction conditions, including the DMSO content in mixed solvents, molar ratio between precursors, growth time, and decoration of dextran, were systematically investigated. Most importantly, it was the union of DMSO and water that achieved the combined merits of both solvothermal and hydrothermal methods, namely, high uniformity and high efficiency, respectively. In addition, numerous properties of these ZIF-8 nanoparticles were subsequently studied, such as the crystal structure, surface properties, and porosity. Furthermore, composite ZIF-8 nanoparticles encapsulating various functional molecules were also successfully prepared in the same DMSO/H2O mixed solvents, thus laying the foundation for their application as nanocarriers in the biomedical field.