Efficient grinding is one of the important means to reduce energy consumption in cement production, and the development of efficient grinding aids based on molecular structure design is currently a research hotspot. In this work, 2-acrylamido-2-methylpropanesulfonic acid (AMPS), hydroxypropyl acrylate (HPA), and diethylene glycol monovinyl ether (DEGVE) as monomers was applied to synthesize a novel low molecular weight polymer. A polymer-based grinding aid for cement clinker was prepared by incorporating polymeric polylol, and its structure-activity relationship was systematically evaluated. The results showed that the optimal performance was achieved when the amounts of initiator and chain transfer agent were 1.39% and 5.84%, respectively, and the ratio of n (DEGVE): n (AMPS): n (HPA) was 1:1.85:0.5. It should be noted that the optimal grinding performance is determined by the D50 value and the 45 µm sieve residue, not by the particle specific surface area or the strength of cement hydration, which are not the primary indicators for evaluating grinding performance. Compared with alcohol amine grinding aids, the prepared grinding aid could significantly optimize particle size distribution of cement. The volume fraction of particles above 0-32 µm and 64 µm was decreased by 1.5% and 51.7%, respectively, while increased by 59.5% for 32-64 µm; Compared with the alcohol amine grinding aid, the compressive strength of cement at 3 d and 28 d increased by 3.4% and 8.3%, respectively.