The simultaneous occurrence of iron, manganese and antibiotics within groundwater enhances the difficulties for drinking water treatment. In this study, the peroxymonosulfate (PMS)-assisted in-situ oxidation/coagulation(O/C) coupled with ceramic membrane process was employed to remove the iron (Fe2+: 2.0–4.2 mg/L), manganese (Mn2+: 0.99–4.12 mg/L), and antibiotics (Sulfamethazine(SMZ) = 400–800 µg/L) simultaneously. The results indicated that Fe2+ existing in groundwater was able to in-situ active PMS for producting hydroxyl radicals (OH) and sulfate radicals (SO4−), oxidizing antibiotics or natural organic matter (NOM) together with manganese and ferrous. Subsequently, through scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS) and laser scattering particle analyzer (LSPA), it was found that the aggregates (264–685 µm) generated by oxidation/coagulation process were effectively rejected by ceramic ultrafiltration membrane. Besides, membrane filtration performance depended strongly on the crystallization structure of aggregates. The X-Ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis demonstrated that NOM in groundwater weakened the crystallization of ferric hydroxides or manganese precipitation, diminishing membrane filtration efficiency. Based on the outstanding performance of in-situ O/C, this integrated process exhibits considerable potential application in the treatment of groundwater, and the highlight was that ferrous within groundwater could be utilized to active PMS in-situ.