Mannosylerythritol lipids (MEL) are glycolipids mainly produced by pseudo-yeasts. These molecules present remarkable biological activities widely explored in many fields, including medicine, pharmaceuticals, and cosmetics. This review presents the main biological activity of MEL on the HL60, K562, B16, PC12, and skin cells. There is strong evidence that MEL changes the levels of glycosphingolipids of HL-60 lineage, which induce differentiation into granulocytic cells. Regarding B16 cells, MEL can trigger both apoptosis (10 μM) and cell differentiation (5 μM), in which the MEL concentration is related to each metabolic pathway. MEL can also trigger differentiation in PC12 cells due to the increase in the GalCer content. In this specific case, the effects are transient, and the differentiated cells are unstable and tend to apoptosis. MEL-B can particularly maintain skin hydration and moisture due to their self-assembled structures that resemble the tissue cells. Moreover, MEL-B repair aquaporin expression in the HaCaT keratinocytes damaged with UVA irradiation, whereas MEL-C suppresses the expression of COX-2 protein in fibroblasts, indicating that these glycolipids activate the cellular antioxidant mechanism. Recent findings denoted the anti-melanogenic activity of MEL since they suppress tyrosinase enzyme at mRNA levels in B16 and NHMs cells. MEL act effectively on mammalian cells; however, there is no clear pattern of their metabolic effects. Also, gene expression levels seem to be related to two main factors: chemical structure and concentration. However, the specific signaling cascades that are induced by MEL remain inconclusive. Thus, further investigations are vital to understanding these mechanisms clearly. KEY POINTS: • The four MEL homologs promote different biological responses in mammalian cells. • MEL modifies the pattern of glycosphingolipids in the plasma membrane of tumor cells. • Activation/deactivation of phosphorylation of serine/threonine kinase proteins.