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Background: The genus Piper L. has the shikimic acid pathway predominantly expressed, biosynthesizing many cinnamic acid derivatives (CAD). Objective: Neolignans comprise an important class of CAD that exhibit a wide range of pharmacological properties such as antibacterial, antitumor, insecticidal, anti-inflammatory, antioxidant, smooth muscle relaxant, neuroprotective, antiprotozoal and against platelet aggregation factor. These substances have been extracted and isolated from Piper species using different technics. Results: The present review aims to summarize extraction and isolation methods and biological activities of the different types of neolignans covering the period from 1968 to January 2016.