Although Pereskia grandifolia is a cactus by classification, it takes the form of a shrub or small tree, 2-5 metres (6.6-16.4 ft) in height. It has a grayish-brown trunk up to 20 cm in diameter. The areoles are rounded cushion-shaped grayish or brownish tomentum; on the twigs they are 3-7 mm diameter and up to 12 mm on the main trunk. The spines range from black to brown, the number at each areole gradually increasing with age; new twigs can have spineless areoles, while the trunk areoles may have up to 90 spines, each 2-6.5 cm long.
The leaves vary in size from 9-23 cm long, entire, with shapes ranging from elliptic to ovate and obovate-lanceolate.
The dense inflorescence develops at the ends of stems, usually with 10-15 flowers, but sometimes with 30 or more. The flowers are showy and rose-like, 3-5 cm in diameter.