A paleobiological study of Santacrucian native ungulates is presented in this chapter. Seven families are recorded: Hegetotheriidae, Interatheriidae, Toxodontidae, and Homalodotheriidae (Notoungulata); Proterotheriidae and Macraucheniidae (Litopterna); and Astrapotheriidae (Astrapotheria); however, a detailed systematic revision is still pending. A broad body size range is recorded. Typotheres (Hegetotheriidae + Interatheriidae) vary from 2 to 10 kg, proterotheriids vary from 20 to 100 kg, toxodonts and macraucheniids surpass 100 kg, and astrapotheres reach 1000 kg. The highest taxonomic richness corresponds to the range between 20 and 100 kg. Locomotor behavior is interpreted as mostly cursorial. Typotheres might have engaged in occasional digging, but this group also includes the most agile and fastest forms, more so than proterotheriids. Only two taxa in the sample (Interatherium and Astrapotherium) show evidence of swimming capabilities and potential aquatic habits. In contrast, feeding behavior presents less variation, which agrees with previous interpretations: notoungulates inhabited open habitats and fed mainly on grass, while litopterns and astrapotheres inhabited closed habitats and were mainly browsers. We infer that notoungulates had exceptional chemical digestion capabilities whereas litopterns may have relied on long periods of chewing to process their food.