Granulation is an effective method for improving the flowability of drugs, particularly when they are in needle form. Carbamazepine-hesperetin (CBZ-HPE) cocrystal is a needle-like crystal with low solubility and poor flowability, which limits its application. To address this issue, this study aimed to obtain CBZ-HPE microspheres using the quasi-emulsion solvent diffusion (QESD) technique. The preparation process was monitored using polarized light microscopy, and the formation mechanism was elucidated using the radial distribution function (RDF). The microspheres were extensively characterized using PXRD, DSC, TGA, and SEM. Furthermore, the effects of surfactants, contents, and rotational speeds on the morphology and particle size distribution of microspheres were analyzed to determine the optimal experimental conditions. Based on these findings, naringenin and quercetin, the active ingredients of traditional Chinese medicine, were chosen to successfully prepare CBZ-HPE multicomponent microspheres. This research provides a foundation for increasing drug powder properties and drug conjugation through the preparation of microspheres.