Efficient adsorbents for radioiodine removal play a crucial role in safeguarding public and ecology health. However, conventional trial-and-error approaches for designing such high-performance adsorbents suffer from limited efficiencies. Herein, we employed a rational design strategy guided by precise density functional theory (DFT) calculations to synthesize a polyphosphazene-based microsphere tailored for iodine capture. Theoretical calculations quantifying the interactions of iodine molecules with diverse nitrogen-containing organic groups reveal the superior affinity of phosphazene groups with I2. Motivated by these findings, we judiciously designed a poly(bis(diethylamino)) phosphazene (PDEP) with a high density of active adsorption sites. Subsequently, PDEP was integrated into a composite bead with polyether sulfone (denote as PDEP@PES) for practical applications. PDEP@PES exhibits an elevated static adsorption capacity of 1.08 g/g, surpassing the majority of reported beads. More importantly, under a high flow rate of 200 mL/min, the dynamic uptake amount of PDEP@PES reaches 78.8 mg/g, outperforming pristine PES beads (3.19 mg/g) and commercial silver-impregnated silica gel (23.0 mg/g). The XPS results confirm the formation of robust charge-transfer complex between phosphazene groups with I2. This was further supported by their substantial interaction energy of -20.59 kcal/mol, as determined by DFT calculations. Our study demonstrates the high feasibility of polyphosphazene-based microspheres for radioiodine removal, shedding light on the enormous potential of theory-driven design paradigm for the development of exceptional adsorbents for environmental remediation.