Little is known about Native American adaptations to blood-sucking arthropods prior to and following European contact. Multiple accounts starting in the 16th century suggest that rancid animal grease was employed by Gulf Coast indigenes as a mosquito repellent. Although many Native American ethnobotanical remedies for biting insects have been recorded, the use of animal products for this purpose is not well documented. Moreover, few traditional Native American mosquito repellents have been examined using controlled laboratory methods for repellency testing. In this study, we tested the repellent efficacy of fats derived from alligator, bear, cod, and shark that were aged to various stages of rancidity. Using yellow fever mosquitoes, (Aedes aegypti), we performed an arm-in-cage assay to measure the complete protection times resulted from these fats, when applied to human skin. We used a Y-tube olfactometer assay to evaluate long-distance repellency and tested tick-repellency in a crawling assay. Our results suggest that rancid animal fats from cod, bear, and alligator are potent albeit short-lived mosquito repellents. We found that both rancid and fresh fats do not repel ticks. Our findings show the validity of traditional ethnozoological knowledge of Native American people and support aspects of the ethnohistorical record.