This study aimed to optimize nutrient sources for enhancing the accumulation of antioxidants in Citrus reticulata peel powder (CRPP) through solid-state fermentation (SSF) using Aspergillus niger CGMCC 3.6189. A Plackett-Burman design revealed that four medium compositions, including yeast extract, NH4Cl, CaCl2, and MgCl2, significantly affected antioxidant accumulation in fermented CRPP. The optimal concentrations of these four compositions were predicted as 13.86, 0.40, 0.06, and 0.04 mg/g of CRPP, respectively, using a Box-Behnken design (BBD) when simultaneous optimization of total phenolic content (TPC), total flavonoid content (TFC), 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging capacities using Derringer's desirability function. Under the optimal medium compositions, TPC, TFC, ABTS, and DPPH scavenging capacities of fermented CRPP (FO-CRPP) increased by 25.2%, 26.9%, 45.8%, and 57.3%, respectively, in comparison with the unfermented CRPP (UF-CRPP). The HPLC analysis exhibited notable decreases in the levels of hesperidin, narirutin, nobiletin, and tangeretin, while enhancements in the contents of p-coumaric acid, ferulic acid, narirutin, and hesperetin in FO-CRPP compared to UF-CRPP were observed. Scanning electron microscopy and Fourier transform infrared spectroscopy analyses demonstrated changes in the surface microstructure and functional groups in FO-CRPP. Our findings suggested that yeast extract and NH4Cl significantly improve the accumulation of antioxidants in CRPP during SSF by A. niger CGMCC 3.6189.