Haskap (Lonicera caerulea L.) berry is enriched in anthocyanins, primarily cyanidin-3-O-β-glucoside (C3G). It remains unknown whether C3G counteracts metabolic alterations of the pathogenesis of obesity. In this study, mice were fed high-fat high-sucrose (HFHS) diet supplemented either with C3G-rich extract (HFHS + CE) or berry powder with low C3G (HFHS + BP). Mice fed HFHS + CE displayed short-term protection against weight gain, independent of food intake. HFHS + CE mice had lower hepatic diacylglycerols and triacylglycerols content and reduced expression of key lipogenic transcription factors. These metabolic changes also translated into improved glucose tolerance and insulin sensitivity. 16S rRNA sequencing revealed altered gut microbiota composition in the HFHS + CE group. In summary, we demonstrate that C3G enrichment in the HFHS diet attenuates short-term weight gain, decreases hepatic lipid content by suppressing key lipogenic gene expression and improves glucose homeostasis during obesity development, supporting the therapeutic utility of C3G as a bioactive phytonutrient to manage obesity-related complications.