Manyoni has over 70 mammal species, including all the Big 5, cheetah, giraffe, zebra, hyena, blue wildebeest, kudu and other smaller antelope. Sitting at 434 recorded species, Manyoni is one of the best birding spots in South Africa, with special varieties including the pink-throated Twinspot, Green Twinspot, African Broadbill, Rudds Apalis and Neergards Sunbird.

The reserve has diverse habitats from rolling grasslands to steep rocky hills, savannah thornveld and riverine forests. It is a Biodiversity Stewardship Reserve, which recognises it as a custodian of shared natural heritage. This is evidenced in Manyoni’s strong focus on conserving and protecting indigenous flora and fauna.