Polyethylene glycol (PEG)-based resins were fabricated using a microfluidic device, enabling the production of monodisperse, core–shell-structured, amino-functionalized particles. The microfluidic generation of microbeads offers a highly efficient and reproducible approach for creating various functional hydrogel beads via water-in-oil emulsion polymerization within a microchannel. We investigated how the swelling behavior, hydrophilicity, and crosslinking density of PEG resins influenced the synthesis of a difficult peptide—the Jung-Redemann decapeptide—and cell adhesion behavior mediated by the RGD peptide motif. Our findings indicated that efficient solid-phase peptide synthesis was closely related to surface dynamics governed by the mechanical properties of the PEG resin. To enhance peptide purity, we optimized the resin formulation by adjusting the acrylated PEG monomer composition. Additionally, PEG resin exhibited superior performance in distinguishing RGD-specific interactions from non-specific binding. These results suggest that PEG resin is well-suited for both solid-phase peptide synthesis and high-stringency biological screening, particularly in cell-targeting applications.