As a natural green catalyst, laccase has extensive application in the fields of environmental monitoring and pollutant degradation. However, susceptibility to environmental influences and poor reusability seriously hinder its application. To address these concerns, for the first time, manganese ion replaced copper ion as the active center to coordinate with guanosine monophosphate (GMP) for synthesizing mimic laccase with high catalytic activity. Compared with natural laccase, the laccase-like nanozyme (Mn− GMPNS) demonstrated superior thermal stability, acid−base resistance, salt tolerance, reusability, and substrate universality. Benefiting from the high catalytic activity of Mn−GMPNS, epinephrine, a significant neurotransmitter and hormone associated with numerous diseases, was visually detected within 10 min and a portable assay by smartphone. More encouragingly, Mn−GMPNS can efficiently degrade dye pollutants, achieving a decolorization rate over 70% within 30 min. Thus, the coordination between manganese ion and nucleotide demonstrated the potential in rational design of nanozymes with high catalytic activity, low cost, good stability, and good biocompatibility.