Penta-O-galloyl-D-glucose (PGG) is a simple hydrolysable tannin in plants. PGG exists in two anomeric forms, α-PGG and β-PGG. While β-PGG can be found in a wide variety of plants, α-PGG is rather rare in nature. Numerous studies with β-PGG revealed a wide variety of biological activities, such as anti-microbial and anti-cancer functions. Until recently, studies with α-PGG were limited by the lack of its availability. Since the development of an efficient chemical synthesis of the compound, several investigations have revealed its anti-diabetic, anti-cancer, and anti-platelet-coagulation functions. Based on structure-activity-relationship (SAR) studies with α-PGG, a variety of α-PGG-related novel compounds were synthesized and some of them have been shown to possess promising therapeutic activities. In this review, the authors will survey and evaluate the biological functions of PGG with a focus on α-PGG and its derivatives.