How can imaging be improved? Coordination polymers (CPs) show fascinating potential in optoelectronic optics but limited potential in bioimaging. Without doubt, it was very meaningful when CPs were first used in second-harmonic generation (SHG) imaging. Herein, through reasonable design and synthesis, a series of nonlinear optical CPs bearing very good one-photon excited fluorescence (OPEF), two-photon excited fluorescence (TPEF) and very strong SHG properties has been presented. Further study demonstrated that the nanoscale CPs show very strong SHG signals which have been applied in the three-dimensional imaging of thick block tissue with higher spatial resolution through simultaneous multichannel nonlinear optical (NLO) imaging technology. After simple encapsulation by polymeric micelles, the nanoscale CPs were successfully applied in SHG bio-imaging within the living cells. This finding throws light on the design of nanoscale NLO CPs and offers a simple avenue to develop novel effective exogenous SHG imaging agents.