Regarding the biological effects of shark cartilage (SC) as well as its anti-angiogenic, immunostimulatory, and anti-inflammatory characteristics, this natural supplement is directly or indirectly marketed as a therapeutic and preventive option for various diseases e.g. cancer and rheumatoid arthritis (RA). In this study, the immunomodulatory effects of SC were reviewed in terms of SC components. Therefore, the effects of total SC without any fractionation were explained and low-molecular-weight protein (LMWP) fraction along with type II collagen (CII) having stimulatory impacts on the immune system were illustrated. Eventually, the immunomodulatory effects of SC proteoglycan (PG) revealed that the given fractions were useful for inflammatory diseases.