Using high-throughput analysis methods, the present study sought to determine the impact of prenatal high-fat dietary manipulations on isolation-induced ultrasonic vocalization production in both male and female <i>Fmr1</i>mutants on postnatal day 9. Prior to breeding, male FVB/129 <i>Fmr1</i> wildtype and female <i>Fmr1</i> heterozygous breeding pairs were assigned to 1 of 3 diet conditions: standard lab chow, omega-3 fatty acid-enriched chow, and a diet controlling for the fat increase. Prenatal exposure to omega-3 fatty acids improved reductions in the number of calls produced by <i>Fmr1</i>heterozygotes females. Moreover, diminished spectral purity in the female <i>Fmr1</i>homozygous mouse was rescued by exposure to both high-fat diets, although these effects were not seen in the male <i>Fmr1</i>knockout. Prenatal dietary fat manipulation also influenced several other aspects of vocalization production, such as the number of calls produced and their fundamental frequency, aside from effects due to loss of <i>Fmr1.</i>Specifically, in males, regardless of genotype, prenatal exposure to high omega-3s increased the average fundamental frequency of calls. These data support the need for future preclinical and clinical work elucidating the full potential of prenatal high-fat diets as a novel therapeutic alternative for<i></i>Fragile X syndrome.