Proanthocyanidin, a natural phytochemical bioactive agent, simultaneously can silence the activity of dentinal proteases and crosslink the collagen matrix; both of these phenomena would be the fundamentals for bio-stability of resin-dentin interface which is essential for a promising adhesive dentistry. This review provides an overview of the data developed by different groups of researchers and highlighted topics are proanthocyanidin chemistry, natural resources and the unique interactions between proanthocyanidincollagen and proanthocyanidin-MMPs in dentin. Besides, clinical applications of proanthocyanidin in the form of proanthocyanidincontaining adhesives, preconditioners and etchants have been reviewed. One hundred and twelve studies have been published in peer-reviewed journals from 1981 to 2017, all were comprised in this review, some of them have been actually proven to be promising from clinical point of view and others need further assessment before their adoption as clinically practicable protocols.