Huangqi (Astragalus spp.) is a versatile herb that possesses several therapeutic effects against a variety of diseases, especially lung diseases. The aim of this study was to establish a core collection of Astragalus germplasm resources based on 10 simple sequence repeat (SSR) markers. We used 380 samples of Astragalus collected from different regions to a core Astragalus collection using five different methods, including PowerCore-based M strategy, CoreFinder-based M strategy, Core Hunter-based stepwise sampling, PowerMarker-based simulated annealing algorithm based on allele maximization, and PowerMarker-based simulated annealing algorithm based on maximizing genetic diversity. Among these methods, the CoreFinder-based M strategy was found to be the most suitable approach as it preserved all the alleles, and most of the genetic diversity parameters of the constructed core collections were higher than those of the initial collection. Additional analyses demonstrated that the genetic diversity of the core collection was similar to that of the initial collection. Further, phylogenetic trees indicated that the population structure of the core collection was similar to that of the initial collection. In addition, our results showed that the optimal grouping value of K was 2. The construction of a core collection is beneficial for the understanding, management, and utilization of Astragalus. Moreover, this study will serve as a valuable reference for constructing core collections of other plants and fungi.