ABSTRACT Suzetrigine (SUZ), an analgesic for acute pain, requires strict enantiomeric purity control. This study develops a robust chiral HPLC method for SUZ and its R‐enantiomer using analytical quality by design (AQbD). Separation was achieved on a Chiralpak IC‐3 column with an isocratic n‐hexane–ethanol (90:10, v/v) mobile phase. The optimized method provided baseline resolution ( R s = 3.0) in 15 min. Validation via the accuracy profile approach confirmed reliable quantification, with limits of 290 μg mL −1 (SUZ) and 0.32 μg mL −1 (R‐enantiomer). The AQbD strategy defined a method operable design region (MODR) ensuring robust routine performance. Furthermore, multimetric sustainability assessments demonstrated a favorable environmental profile, yielding blue applicability grade index (BAGI) and mosaic‐WAC scores of 77.5 and 73.2, respectively. This approach enables reliable, eco‐friendly enantiomeric purity assessment of SUZ in bulk and pharmaceutical formulations.