There are no trees on Santa Barbara Island, and only a few shrubs. The vegetative aspect is that of herbaceous plants and grasses, verdant in the spring and appearing dry and brown in the hot summer. The island supports about 120 different species of plants, about 30% of which are introduced weeds. There are fourteen endemic species or subspecies of plants which occur on Santa Barbara Island and at least one other California Channel Island.

There are three plants restricted to Santa Barbara Island. They are a low shrubby buckwheat (Eriogonum giganteum compactum), a small succulent (Duleya traskiae), and and annual poppy (Platystemon californicus ciliatus).

The sunflower (Asteraceae) and grass (Poaceae) families comprise the largest portion of the flora of this island. Of the 120 different plant species, 30 are in the sunflower family and 22 are grasses.

There is only one terrestrial mammal on Santa Barbara Island. The endemic subspecies of deer mouse (Peromyscus maniculatus elusus). Predators to the mouse include various species of hawks and owls but the deer mouse has no mammalian predators.

Marine mammals common to Santa Barbara Island include California sea lions, harbor seals and northern elephant seals. Otters were a common sight in the early 19th century but due to over hunting they were exterminated from the island.

The island night lizard is the only reptile found on this island. This endemic Channel Island reptile is also found on San Nicolas and San Clemente. The 1973 Endangered Species Act lists this lizard as threatened.

At least seventy types of birds are reported. Among the more interesting are peregrine falcons, California brown pelicans, horned larks, three types of owls, Costa's and Allen's hummingbirds, Xantus' murrelets, Cassin's auklets, and both black and ashy storm petrels. The horned lark, orange-crowned warbler, and house finch are Channel Island endemics.

The endemic Santa Barbara Island song sparrow (Melospiza melodia graminea) is thought to be extinct. In 1959 a fire destroyed much of the bird's habitat and it survived only another eight years.This sparrow was one of the smallest forms of song sparrow, differentiated by its very grey back.