Bioarchaeology, health, and the lived experience: By examining skeletal and dental remains Alfonso-Durruty investigates health, nutrition, growth, childhood, trauma, violence, and biological responses to environmental and social conditions. Her research also examines how skeletal indicators develop and how they can be interpreted, helping refine the methods used to reconstruct the lives of past populations.

Human population history and ancient DNA: Using molecular data Dr. Alfonso-Durruty investigates the peopling of Patagonia and Tierra del Fuego, examining population origins, migrations, genetic diversity, genetic drift, and interactions among ancient hunter-gatherer communities. By integrating ancient DNA with archaeological and biocultural evidence, this work reconstructs population histories and explores how genetic patterns relate to cultural change and social connections.

Diet, subsistence, and human–environment relationships: Alfonso-Durruty's work in northern and north-central Chile explores dietary diversity, foodways, marine resource use, and the relationships between subsistence practices and social organization. These studies investigate how communities adapted to coastal and desert environments, how food practices changed through time, and how political and economic transformations influenced diet and daily life.

Methodological innovation in biological anthropology: Interest in the ethical aspects of bioarchaeological research, as well as questions regarding the validity of some established methods/practices  has led Dr. Alfonso-Durruty to develop and evaluate methods for studying human remains, including dental anthropology, skeletal indicators of physiological stress, age estimation, as well as digital curation and three-dimensional documentation of dental remains. This methodological work strengthens the reliability of biological and archaeological interpretations.