A novel method of generating hydrogel particles for various applications including drug delivery purposes was developed. This method is based on the production of hydrogel particles from sprayed polymeric nano/microdroplets obtained by a nebulization process that is immediately followed by gelation in a crosslinking fluid. In this study, particle synthesis parameters such as type of nebulizer, type of crosslinker, air pressure, and polymer concentration were investigated for their impact on the mean particle size, swelling behavior, and morphology of the developed particles. Spherical alginate-based hydrogel particles with a mean particle size in the range from 842 to 886 nm were obtained. Using statistical analysis of the factorial design of experiment it was found that the main factors influencing the size and swelling values of the particles are the alginate concentration and the air pressure. Thus, it was demonstrated that the method described in the current study is promising for the generation of hydrogel particles and it constitutes a relatively simple and low-cost system.