Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease without an effective and safe treatment. Besides, macrophages are the major components of the innate immune system and play a critical role in the inflammation process in SLE. Secoiridoids from olive tree are phenolic compounds which have shown important pharmacological effects. Particularly, oleuropein (OL) has shown antioxidant, anti-inflammatory and immunomodulatory properties suggesting a potential application in a large number of inflammatory and reactive oxygen species (ROS)-mediated diseases. In addition, different studies have shown the importance of acyl derivatives of natural phenols due to their better hydrophilic/lipophilic balance.