Lactobionic acid (LBA) has rapidly emerged as a strategic functionalization molecule in the development of nanoparticle-based platforms and biomaterials with promising therapeutic applications. Exploiting the multi-functionality of LBA has enabled to expand the drug loading, release and selective cellular uptake capacity of hepatoma-targeting chemotherapy and nanoparticle-based theranostic systems. The high liver-specificity displayed by LBA-conjugated dendrimers, micelles and nanoparticles has indeed reinforced the great potential of LBA in fine-tuning the surface engineering of promising drug carriers to combat hepatocellular carcinoma. Additionally, its cytocompatibility, selectivity and functionality confer unique properties to design synthetically engineered matrices with enhanced liver-specificity for liver tissue engineering applications. Notably, the biospecific identification and biochemical cross-linking specificity found with the asialoglycoprotein receptor (ASGPR) have converted LBA into the perfect cell-targeting ligand for strengthening the recognition between novel designed nanocarriers and hepatocytes at cellular level. The present review overviews the latest advances in the galactosylation of target-specific nanocarriers and polymers via LBA functionalization with an emphasis on the great bioengineering versatility offered by this polyhydroxy bionic acid in the preparation of next-generation tools ranging from contrast imaging agents to galactosylated scaffolds for the diagnosis and treatment of hepatic diseases. Perspectives on the bioengineering approaches that can foster the design of multi-functional LBA-conjugated therapeutic nanoplatforms are also discussed.