Background <p>Fibulins belong to the family of secreted glycoproteins regulating several cellular processes. Fibulin7 (Fbln7) is one of its recent members, and it was first identified in the developing tooth. Fbln7 is also expressed in specialized tissues such as cartilage, eye, and the placenta. Previous reports have suggested that its C-terminal (Fbln7-C) fragment and not the full-length protein can inhibit angiogenesis, and modulate systemic inflammation and cancer.</p> Method <p>We have performed a literature review based on published original and review articles that encompass the significant effect of Fbln7 and its bioactive fragments on immune cell functions from central databases, including PubMed and Google Scholar.</p> Results and Conclusion <p>Recent reports have also shown that several shorter peptides of Fbln7-C, such as FC-10, regulate innate immune cell functionality and have anti-angiogenic properties. Since the discovery of Fbln7, many research groups have improved our understanding of the role of Fbln7, Fbln7-C, and short peptides in immunoregulation and pathophysiology of many disease conditions, such as sepsis, kidney injury, and different cancers (e.g., murine breast tumors and glioblastoma). This review will present an updated overview of the research findings on the immunomodulatory, anti-angiogenic, and other regulatory properties of Fbln7 and its fragments, which will provide further insight into its significance, mode of action, and possible implications for future research and therapeutics.</p>