Polydimethylsiloxane (PDMS) microparticles exhibit significant potential for biomedical applications owing to their biocompatibility,

chemical inertness, transparency, and ease of soft lithography-based fabrication. However, their high viscosity

and hydrophobicity make it difficult to use them in the form of particles in aqueous environments. In this study, we present

a novel and efficient methodology for fabricating uniform PDMS microparticles using a discontinuous dewetting (DD)

technique. Our approach employs a polyethylene glycol diacrylate mold coated with a superhydrophobic layer, enabling DD

over a broad viscosity range and achieving highly monodisperse particle production. To utilize them in an aqueous solution,

we implemented two surface modification strategies: a bovine serum albumin (BSA) treatment, and the formation of

“hydrogel skin”. Such strategies enhance their water wettability and the particle’s dispersion in an aqueous solution. Our

findings demonstrate the successful fabrication of monodisperse PDMS microparticles with diameters ranging from 200 to

1000 μm, which were well dispersed in organic or aqueous solutions. Our research would suggest a new strategy for how to

use PDMS in bioengineering. We anticipate that our PDMS microparticles offer significant potential in diagnostic, chemotaxis,

and therapeutic applications.