In recent years, Meteorin-like protein (Metrnl/IL-41) and Follistatin-like 1 (FSTL1) have emerged as multifunctional molecules that play roles in immunity, metabolism and tissue remodeling. Although they demonstrate pleiotropic effects, they are promising candidates for biomarkers and possible therapeutic targets. The development of new, disease-specific biomarkers will enable clinicians to more effectively monitor inflammatory activity, more accurately assess disease severity, better predict survival, and select appropriate medical treatments. In this review, we present the role of Meteorin-Like Protein (Metrnl) and Follistatin-like 1 (FSTL1) in inflammation in autoimmune rheumatic diseases, as well as in other autoimmune pathologies, cardiovascular diseases, and metabolic diseases. Metrnl, widely expressed in different tissues and organs, is very important for inflammation, immune responses and metabolic disorders. FSTL1 also shows dynamic changes in its expression through various diseases, including cardiovascular conditions, cancer, asthma, and arthritis. Both proteins participate in multiple important signaling pathways, and understanding their diagnostic and therapeutic potential holds great scientific interest. Their complex nature requires careful evaluation of safety concerns and translation to clinical practice.