Because Guaramacal is part of the Northern Andean biogeographical region, there is a large number of endemic animal and plant species. It seems that the cloud rainforests of this mountainous region were separated from the rest of the Merida Range by the arid zone of Boconó River canyon, which served as an ecological barrier during the last glacial period (Garcia-Perez, 1992).
Guaramacal's herpetofauna include 14 amphibian species and 11 reptile species. An endemic salamander (Bolitoglosa sp.) and 12 toad and frog species represent the amphibians. The frogs and toads are from the Leptodactilydae, Dendrobatidae, Hylidae, Centronelidae and Bufonidae families. An endemic species of toad, Colostethus humilis, stands out because the adults care for the eggs until they hatch. Very recently, researchers have discovered several new species and are still in the process of describing them. Such is the case of the following toads: Atelopus sp., Eleutherodactylus sp., Leptodactylus sp., Mannoprhynne sp., and Colostethus sp. Guaramacal has 7 snake species and 4 lizard species. Researchers believe that two tree-dwelling lizards of the genus Anolis and Phenacosaurus and one venomous rattlesnake, Bothrops sp., could be endemic to the park. It is estimated that about 40% of the reptile species and amphibian species found in the Massif of Guaramacal are regional endemics (Garcia-Perez, 1998).
Guaramacal has 150 avian species, with both Andean and Coastal Range distribution. Some of these species are threatened or endangered, like the helmeted curassow (Pauxi pauxi), which is one of the most endangered cracids, and the black-billed mountain toucan (Andigena nigrirostris). Venezuelan law prohibits poaching of this toucan. The status of the isidor's eagle (Oroaetus isidori) is uncertain, but it is believed that this species is also threatened. There are also several rare bird species and species whose distribution in the area have only recently been discovered, such as the Pyrrhura rhodocephala (endemic to the Venezuelan Andes), the Haplospiza rustica, Acropternis orthonix, Glaucidium jardinii and Pandion haliaetus.
Mammal studies done in Guaramacal document the presence of 7 orders, 15 families and at least 36 mammal species (Utrera, 1998). Bat diversity is impressive; there are 16 species inside the park, some of which are insectivores (Eptesicus brasiliensis, Lasiurus ega and Myotis oxiotus). Rodent diversity is also notable; there are 8 species in the park: Heteromys nomalus, Neacomys tenuipes, Oryzomys albigularis, Mycroryzoyis miutus, Aepeomys schistaceus, A. lugens, Thomasomys laniger and Agouti taczanowskii, the last four species have distributions restricted to the Andes. The agouti (A. taczanowskii) is endangered and hunting is prohibited.
Common mammals include the sloth (Bradypus variegatus), white-eared opossum (Didelphis albiventris), red howler monkey (Alouatta seniculus), and kinkajou (Potos flavus). Other species listed in Venezuelan's red book of threatened species are a local species of brocket deer (Mazama bricenii), which needs protection because of high hunting pressure, mountain coati (Nassuela olivacea), olingo (Bassaricyon gabbii), puma (Puma concolor) and spectacled bear (Tremarctos ornatus), which is the only member of the Ursidae Family in South America. Cryptotis meridensis is also present in Guaramacal and it is the only representative of the Insectivora Order in Venezuela.
Park vegetation is diverse and consists of 147 families, 517 genera and 1,227 species. Using samples taken from this park, 33 taxa have been described for science and most of them are endemic to the park. Some of the park endemic floras are two ferns (Elaphoglossum apressum and E. delicatum), several orchids (Trichosalpinx deceptroix, T. dunstervillei, Lephantes glochidea, L. scolex), Melastomataceae (four species of the genus Miconia) and some Solanaceae. The best represented families are Orchideaceae (115 species), Asteraceae (102), Rubiaceae (73), and Piperaceae (46). The genera Elaphoglossum, Peperonia and Miconia each have 26 species.
