Female germline stem cells (FGSCs) and spermatogonial stem cells (SSCs) are germline stem cells that transmit the genetic material from generation to generation. Hence, it is essential to understand the similarities and differences between FGSCs and SSCs. In this study, we comprehensively compared the epigenetics of FGSCs and SSCs, including high-orderchromatinorganization, chromatinhistone modification, and transcriptome by analyzing multipleomics data (Hi-C, ChIP-seq, and RNA-seq). We found that FGSCs and SSCs had both similar and different chromatin histone modifications that were correlated with their chromatin organization. We also identified cell-specific enhancerepromoterinteractionsinFGSCsandSSCs. Furthermore, we found that the X chromosome was similar in FGSCs and SSCs by principal component analysis of the X chromosome. By using RNA fluorescence in situ hybridization (RNA FISH) to confirm the inactivation of the X chromosome in FGSCs, we compared the high-order chromatin structure between activated and inactivated X chromosomes in FGSCs. In summary, we performed a systematic comparison analysis of the epigenetics between FGSCs and SSCs from multiple perspectives using multiple-omics data.