Non-graphitic nitrogen-doped nano-scale diamonds were tested in the laboratory for their ability to activate peroxydisulfate for treating Microcystis-laden water. Flocculation was observed and up to 99.8% of the cyanobacterial cells were removed. The flocs’ composition showed that nano-scale diamonds with activated persulfate promoted the release of protein-like and humic-like substances during the treatment, which could have promoted agglomeration. Comprehensive analyses suggest that both radical and radical-free mechanisms were involved. Extracellular substances associated with the Microcystis cells were modified to function as active bioflocculants, leading to self-flocculation and sedimentation.