In this study, Fe(III) was successfully loaded on the β-Lactoglobulin amyloid fibrils (Fe(III)@β-LGAF) by the in-situ method for efficiently activating peroxydisulfate (PDS) to remove organics in water. Methyl orange (MO) was used as the model contaminant to explore the influences of key parameters in the Fe(III)@β-LGAF/PDS system, including the Fe(III)@β-LGAF dose, PDS dosage, initial MO concentration, and beginning pH value. The results indicated that 94.2% MO was eliminated within 20 min under the optimized conditions of 1 g/L Fe(III)@β-LGAF, 1 mmol/L PDS, 30 mg/L MO, and pH 5. The synthesized Fe(III)@β-LGAF manifested a certain excellent stability and applicability for the PDS activation and other typical organic pollutants degradation. Various characterization methods were applied to characterize the properties of Fe(III)@β-LGAF before and after the oxidation reaction. The radical scavenging test and electron paramagnetic resonance analyses testified that singlet oxygen was the dominant active species in the synergistic process, which exhibited a stronger selective oxidation capacity than the hydroxyl and sulfate radicals. Hence, the synthetic material Fe(III)@β-LGAF could provide a new reference for the heterogeneous Fenton-like reaction.