Background Organ crosstalk can be defined as the complex and mutual biological communication between distant organs mediated by signaling factors. Normally, crosstalk helps to coordinate and maintain homeostasis, but sudden or chronic dysfunction in any organ causes dysregulation in another organ. Many signal molecules, including cytokines and growth factors, are involved in the metabolic dysregulation, and excessive or inappropriate release of these molecules leads to organ dysfunction or disease (e.g., obesity, type 2 diabetes). Aim and method The aim of this review is to reveal the impact of organ crosstalk on the pathogenesis of diseases associated with organ interactions and the role of inflammatory and fibrotic changes in the organ dysfunction. After searching in MEDLINE, PubMed and Google Scholar databases using 'organ crosstalk' as a keyword, studies related to organ crosstalk and organ interaction were compiled and examined. Conclusion The organ crosstalk and the functional integration of organ systems are exceedingly complex processes. Organ crosstalk contributes to metabolic homeostasis and affects the inflammatory response, related pathways and fibrotic changes. As in the case of interactions between adipose tissue and intestine, stimulation of inflammatory mechanisms plays an active role in the development of diseases including insulin resistance, obesity, type 2 diabetes and hepatic steatosis. The increased level of knowledge about the 'crosstalk' between any organ and distant organs will facilitate the early diagnosis of the disease as well as the management of the treatment practices in the short- and long-term organ dysfunction.