In this study, the effects of molecular structure parameters of polycarboxylate ether (PCE)-based grinding aids (GAs) on grinding efficiency, cement properties, and powder flowability were systematically investigated. Existing literature indicates that only limited attention has been given to a comprehensive evaluation of the combined influence of PCE molecular weight, main chain-to-side chain ratio, and side chain characteristics on the grinding process and powder behavior. Within this framework, seven different PCE-based GAs were synthesized by systematically varying the main chain length, side chain length, and side chain/main chain ratio. The structural characterization of the synthesized additives was carried out using Fourier transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC). Subsequently, the grinding efficiency, particle size distribution (PSD), and powder flowability of cements produced at two different GA dosages were evaluated in detail. The results demonstrated that increasing the GA dosage generally enhanced grinding efficiency and led to a narrower particle size distribution. An increase in main chain length at a constant side chain length improved grinding performance, whereas PCEs with a medium main chain length exhibited superior powder flowability. In contrast, increasing the side chain length alone had a limited effect on grinding efficiency. Considering all structural parameters collectively, the PCE5 additive—characterized by medium main and side chain lengths and a low side chain/main chain ratio—exhibited the most balanced and overall highest performance.