Polycarboxylate superplasticizer (PCE) is sensitive to the clay present in concrete aggregates. In particular, Montmorillonite (Mnt), an impurity inevitably contained in the aggregate, can significantly influence the performance of concrete. In an effort to improve the compatibility of PCE, a zwitterionic PCE with cationic amide groups and shorter side-chain lengths was synthesized via free radical copolymerization. The optimal synthesis condition was verified via Box-Behnken design. In addition to characterizing the PCE, the performance of PCE in cement pastes with or without Na-Mnt was examined and the underlying mechanism was explored. The results show that, compared with commercially available PCE, the required dosage of PCE for cements containing Na-Mnt decreased. Unlike commercially available PCE, no intercalation occured on the newly manufactured clay-tolerant PCE within the layers of Mnt, resulting in a greater sorption thickness and improved dispersion of the cements containing Na-Mnt.