Understory species include vines such as rotan (Calamus manan), shrubs such as simpur (Dilenia grandifolia) and albizia (genus Paraserianthes), and grasses like bamboo (Bambusa sp.).

[25] Isau-Isau's rainforest is home to many species of primates: siamang (Symphalangus cyndactylus), southern pig-tailed macaque (Macaca nemestrina), black-crested Sumatran langur (Presbytis melalophos), Sunda slow loris (Nycticebus coucang), and agile gibbon (Hylobates agilis).

Herbivores such as Sumatran porcupine (Hystrix brachyuran), lesser mouse-deer (Tragulus kanchil), sambar deer (Cervus unicolor), southern red muntjac (Muntiacus muntjak), banded pig (Sus scrofa vittatus), Sumatran serow (Capricornis sumatraensis), and Malayan tapir (Tapirus indicus) browse the flora, while the critically endangered Sunda pangolin (Manis javanica) feeds on insects.

[1][2][9][5][26] The reserve is home to the world's rarest lagomorph, the Sumatran striped rabbit (Nesolagus netscheri).

[2] Predatory mammals of the reserve include the binturong (Arctictis binturong), Asian golden cat (Catopuma teminckii), marbled cat (Pardofelis marmorata), Asian leopard cat (Felis bengalensis), dhole (Cuon alpinus), Sunda clouded leopard (Neofelis diardii), sun bear (Helarctos malayanus), and Sumatran Tiger (Panthera tigris sumatrae).

Common species include the crab-eating frog (Fejervarya cancrivora) and Asian giant toad (Phrynoidis asper).

[13] The white-backed bug-eyed frog (Theloderma licin), an IUCN data deficient species, lives in shrubs and on the ground near water sources.

As the human population surrounding the reserve grows and the local environment shifts, there is increasing pressure on the landscape.

[13] Until recently, conservation measures were poorly enforced by authorities due to low budgets following Indonesia's decolonization.

[35] In the 2010s and 2020s, the BKSDA and several non-governmental organizations (NGOs) have begun a series of efforts to protect and restore the ecology of Isau-Isau and other nature reserves in South Sumatra.

[36] A follow-up action plan in 2017 called for increased law enforcement to mitigate illegal logging and poaching.

This plan also called for flora and fauna reintroduction, ecotourism development, renewal of sustainable agroforestry using traditional knowledge, and normalizing biodiversity considerations into everyday life.

Programs such as the Jungle Library Book Project engage children from local villages in hands-on environmental education, where students use scientific exploration to interact with the rainforest.

All students showed improved knowledge of ecological concepts and conservation awareness following their year in the program.

[1][41] The Flora Rescue Project recovers threatened plants from areas of the rainforest that are vulnerable to destruction.