By using a strategy of introducing two organic ligands with different donor groups, two new Cu(II) and Cd(II) coordination polymers (CPs) [Cu3(OH)(pz)3(Hpz)(H2O)(ipa)](H2O)4 (1, Hpz = pyrazol, H2ipa = isophthalic acid) and [Cd(phen)(ndc)](H2O) (2, phen = 1,10-phenanthroline, H2ndc = 1,2-naphthalene dicarboxylic acid) are synthesized and characterized. The molecular structures of the as-prepared CPs were determined by the single crystal X-ray diffraction (SCXRD) studies and their phase purities have been confirmed via the power X-day diffraction analysis (PXRD). The Cu(II)-based complex 1 is composed of trinuclear Cu3(µ3-OH)(pz)3 clusters that extended by the ipa2− ligands into a 1D left-handed helical chain along the c axis. In complex 2, the ndc2− ligands connect with the binuclear Cd2 unit along the c axis to shape a 1D chain-like structure, which is further stacked into a 2D layered network via π–π stacking. The as-prepared two CPs transformed to the nanoscale regime by mechanical grinding to yield nano 1 and nano 2 with excellent water dispersibility, maintaining its crystallinity. In addition, the in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were conducted on the gastric cancer cell line AGS with increasing concentrations of the two nanosized CPs, which reveal their promising anticancer activity.