With the discovery that thalidomide-like drugs induce the ubiquitination and degradation of target effector proteins, drug development based on similar mechanisms, such as proteolysis targeting chimera (PROTAC), has rapidly expanded worldwide, occupying a considerable proportion of the novel drug discovery landscape. As the first clearly identified effector proteins of thalidomide-like drugs, the Ikaros family has also garnered broader attention. Although recent research on this family continues to focus on the development and differentiation of immune cells, a particular shift in interest has been observed toward regulatory T cells (Tregs). Correspondingly, thalidomide-like drugs are now being explored for use in autoimmune diseases, such as systemic lupus erythematosus. As transcription factors, the regulatory mechanisms of Ikaros family proteins have long been a research hotspot. Among various findings, the role of Ikaros in organizing genomic spatial architecture stands out as particularly prominent. Here, we first briefly review the research progress on thalidomide-like drugs, and then summarize newly discovered physiological functions and molecular regulatory mechanisms of Ikaros family proteins. By organizing and analyzing this information, we aim to clarify trends in related research and explore potential strategies for further targeting the Ikaros protein family.