BACKGROUND: Despite the pleiotropic role of resistin as an adipokine, its association with frailty-an indicator of biologic age and overall well-being in humans-remains largely unexplored. This study aims to investigate the potential of circulating resistin as a biomarker for frailty. METHODS: The study included 228 older adults aged 65 years or older who underwent a comprehensive geriatric assessment. Frailty was evaluated using both the phenotypic frailty model by Fried and the deficit-accumulation frailty index (FI) by Rockwood. Serum resistin levels were measured using a competitive enzyme-linked immunosorbent assay. RESULTS: After adjusting for sex, age, body mass index, smoking, alcohol, exercise, diabetes, and serum creatinine, serum resistin levels were 52.2% higher in individuals with phenotypic frailty than in robust controls (P = 0.001) and showed a positive correlation with the Rockwood FI (P = 0.015). Furthermore, for every 1 standard deviation increase in serum resistin levels, the risk of frailty increased by 67% (P = 0.021). When participants were divided into four groups based on serum resistin levels, individuals in the highest quartile had a 38% higher FI and exhibited a 12.5-fold higher odds ratio for frailty compared to those in the lowest quartile (P = 0.016 and 0.024, respectively). CONCLUSION: These findings suggest that circulating resistin may serve as a candidate blood-based biomarker for frailty, encompassing the multifaceted physical, cognitive, and social dimensions, extending beyond its well-established role in metabolic regulation.