Treatment of human urine is an emerging approach to minimize environmental pharmaceutical contamination. This study investigated the application of ferrate(VI) (Fe VI O 4 2−, Fe(VI)) oxidation to degrade pharmaceuticals (i.e., carbamazepine (CBZ), naproxen (NAP), sulfamethoxazole (SMX), and trimethoprim (TMP)) in synthetic hydrolyzed human urine, with the emphasis on the effects of urine endogenous organic metabolites. Creatine and hippuric acid showed limited to moderate scavenging effects. Creatinine (CRE) was first discovered to significantly enhance the oxidation rates of CBZ, TMP, SMX, and other amine-containing compounds by Fe(VI). Fe(IV) was proposed as the major intermediate reactive iron species in the Fe(VI)−CRE system, based on the DFT calculation and experimental measurements. A kinetic model involving Fe(IV) contribution in the decay of the pharmaceuticals was developed for the first time to successfully describe the pharmaceutical removal in the Fe(VI)−CRE−micropollutant system. Moreover, the model was used to predict the rate constants of Fe(IV) reacting with different compounds, which ranged from (2.2 ± 0.1) × 10 4 to (8.3 ± 0.6) × 10 4 M −1 s −1 . Overall, this study further demonstrated the promise of Fe(VI) oxidation to degrade pharmaceuticals in hydrolyzed urine owing to the enhanced effects from urine constituents. This study also advanced the mechanistic and kinetic understanding of enhanced oxidation involving highvalent iron intermediate species.