Aerobic granules synthesized by feeding real wastewater (R-granules) in a sequencing batch reactor were applied to remove Ni2+ and Cd2+ from aqueous solutions and compared with granules cultivated with laboratory-synthesized wastewater (S-granules). Metal biosorption was related to solution pH, initial metal concentration, and reaction time. The chemically modified R-granules showed increased removal efficiency for the examined metals, and the results were almost identical to those of S-granules. Ion-exchange and complexation with extracellular polymeric substances were the predominant mechanisms involved in Ni2+ and Cd2+ loading onto the granules, whereby different groups were associated with the binding. The oxygen atom in peptide bonds interacted more with heavy metals than the nitrogen atom.