Natural products are used in the treatment of numerous human ailments since the inception of life on earth. Pycnogenol (PYC), a standard extract is obtained from Pinus pinaster (P. maritime). The United States Pharmacopoeia describes the characteristic properties of the PYC. Chemically, PYC contains distinct units of epicatechin and catechin. Additionally it comprises of polyphenolic units, cinnamic or phenolic acids along with their glycosidal compounds. Due to the remarkable bioavailability of PYC, it finds application as dietary supplementation and in the management of various disorders of respiratory tract, cardiovascular system, reproductive system and so forth. Moreover, it finds application in mitigation of migraine, obesity, diabetes, osteoarthiritis, urinary tract infection and COVID-19. PYC seems to provide the therapeutic effect due to its anti-oxidant potential owing to the presence of flavonoids, polyphenolic compounds and phenolic acids. The individual components of PYC serve to act in a synergistic manner to provide beneficial effects in human ailments and prevent from the side effects that the individual sub-units might have caused. The current review appraises the pharmacological potential of Pycnogenol paying specific emphasis on its clinical studies and its mechanistic approach.