Inflammation involving the innate and adaptive immune systems is a normal response to infection. However, if it becomes uncontrolled, inflammation may result in autoimmune or auto inflammatory disorders, neurodegenerative diseases or cancers. The currently available anti-inflammatory drug therapy is often not successful or induces severe side effects. Thus, the search of new therapeutic options for the treatment of inflammation is highly required. Medicinal plants have been an interesting source for obtaining new active compounds. Diarylheptanoids characterized by a 1, 7-diphenylheptane structural skeleton, are a class of secondary plant metabolites that have gained increasing interest over the last few decades due to a wide variety of biological activities. This review covers 182 natural linear or macrocyclic diarylheptanoids described in the period of 1982 to 2020 with anti-inflammatory activities evaluated using quantified in vitro and/or in vivo assays. All of these data highlight the pharmacological potential of these natural compounds to act as anti-inflammatory drugs.