Maternal unbalanced diets cause adverse metabolic programming and affect the offspring's liver microRNA profile. The liver is a site of β-carotene (BC) metabolism and a target of BC action. We studied the interaction of maternal Western diet (WD) and early-life BC supplementation on the epigenetic remodeling of offspring’s liver microRNAs. Mouse offspring of WD-fed mothers were given daily a placebo (controls) or BC during suckling. The liver miRNAome was analyzed in recently weaned animals by microarray hybridization. BC impacted the liver miRNAome differently in male and female offspring, with no overlap in differentially expressed (DE) miRNAs between sexes and more impact in females. Bioinformatic analysis of DE miRNA predicted target genes revealed enrichment in biological processes/pathways related to metabolic processes, regulation of developmental growth and circadian rhythm, liver homeostasis and metabolism, insulin resistance, and neurodegeneration, among others, with differences between sexes. Fifty five percent of the overlapping target genes in both sexes identified were targeted by DE miRNAs changed in opposite directions in males and females. The results identify sex-dependent responses of the liver miRNA expression profile to BC supplementation during suckling and may sustain further investigations regarding the long-term impact of early postnatal life BC supplementation on top of an unbalanced maternal diet.