The clam Macridiscus multifarius is ecologically and economically important in the coastal regions of China. In this study, the IIB-RAD method was used to investigate the population diversity and structure of M. multifarius along the coast of China. Genomic DNA was extracted, sequenced, and subjected, resulting in 110.88 Gb of clean reads. Analysis showed that the M. multifarius populations along the coast of China exhibited a moderate to high level of genetic diversity (mean: HO = 0.272, HE = 0.365, π = 0.390, and FIS = 0.268). Further analysis of high-quality single nucleotide polymorphisms was used to generate a maximum-likelihood phylogenetic tree, principal component analysis, and FST values. The results revealed that there is no notable genetic differentiation among the nine M. multifarius populations south of the Yangtze River estuary. However, the Yancheng population shows clear genetic differentiation compared with the other nine populations, possibly linked to the barrier effect of the Yangtze dilution water and ocean current system. We believe that these results provide genetic insights for fisheries management to plan fisheries policies for M. multifarius and conserve natural resources.