Madikwe Game Reserve sprawls across richly varied habitats, from rocky peaks, across open grasslands, to verdant valleys, each zone with it's own distinctive inhabitants. The reserve is home to an astounding array of animal species, from the stately giraffe to the appealing honey badger. The second largest population of elephants in South Africa is found here, as well as a thriving population of the rare and fascinating wild dog.

Lions laze on Madikwe's wide plains, as zebra and blue wildebeest keep a wary distance. Both black and white rhino can be seen in Madikwe and herds of buffalo wander through the wooded areas of the reserve. The elusive leopard may be spotted sleeping on the limb of a tree, while comical warthogs forage in the undergrowth below.

Vast herds of impala graze across the grasslands while cheetah watch from a raised position beside one of Madikwe's distinctive red termite mounds. Regal kudu browse in the cool of the trees next to the river, while Gemsbok and Springbok make their way down to the water. As night falls, the nocturnal creatures of Madikwe begin to stir. The rare brown hyena may be seen foraging for food, while the African civet and the unusual aardvark may also be spotted after dark.

The Madikwe Game Reserve is a bird watchers' paradise, with over 340 species listed here. These include many species of raptor, such as the Martial Eagle, the African Fish Eagle, the Secretary Bird and the Pale Chanting Goshawk. Spotted Eagle Owls are common here, as is the tiny Pearlspotted Owl.

Larger species include the Kori Bustard and the Ostrich while the Lilacbreasted Roller and the Woodlands Kingfisher are amongst the most colourful. The African Finfoot and the Whitefaced duck can often be seen on the river flowing past Makanyane Safari Lodge.

Reptile species represented in the reserve include the African crocodile, Water and Rock monitors, Leopard tortoise, chameleon, the African Rock python and many other species of snake.

The reserve also has a thriving frog population with species like the Banded Rubber frogs, Bubbling cassinas and Foam Nest frogs all being common.