The natural vegetation of the region consists of broad leaved forests (cloudy and rainy), mixed pine-oak and conifer forests. Xeric Association can be found in the shore region of the lake, with characteristic animals and vegetation.
Furthermore, 798 different plant species occur in the region, 61 of them are endemic. The rich biodiversity includes also animal species: 116 species of reptiles and amphibians, 12 species of them are endemic, such as the Salamander species Bolitoglossa franklini, B. flaviventris, B. flavimembris, B. engelhardtii and Oedipina stenopodia. and other species such as Arboreal Alligator Lizard (Abronia matudai) or Botriechis bicolor. In the RUMCLA live 30 % of lizards, 40 % of snakes, 36 % of amphibians registered in Guatemala.
236 bird species are found there, 28 % of them are listed in the Red List of Threatened Species (67 in total), and 12 species are endemic or from restricted areas: Pink-headed Warbler (Ergaticus versicolor), Brown-backed Solitaire (Myadestes occidentalis), the national bird of Guatemala Resplendent Quetzal (Pharomachrus mocinno), Blue-throated Toucanet (Aulacorhynchus prasinus), Atitlan Grebe (Podylimbus gigas), Azure-rumped Tanager (Tangara cabanisi) and Horned Guan (Oreophasis derbianus). Many migratory birds use Lake Atitlán as a wintering ground: Pied-billed Grebe (Podylimbus podiceps), Ruddy Duck (Oxyura jamaicensis) and American Coot (Fulica Americana). Roadrunners (Geococcyx velox), which are typical for Xeric Associations occur in the region as well.