Liver disease is a significant global health issue that affects the liver and contributes to approximately 2 million deaths worldwide each year. Although treatment options including surgery and medication are available, effective treatment remains a challenge because of limitations of the traditional drug-delivery methods, such as uneven and nonspecific drug distribution, which lead to negative effects on healthy tissues and a reduction in drug bioavailability. Nanotechnology provides a promising solution for targeted drug delivery to the liver, which has unique anatomical and physiological structures that render it an ideal target for nanomedicine. Several categories of nanomaterials, including inorganic nanomaterials, polymer nanomaterials, and multifunctional nanoparticles (NPs), have been studied as potential agents for targeting this organ in the context of liver diseases. Using surface modification and functionalization, nanomaterials can be selectively targeted to liver tissue or hepatocytes, thus delivering drugs, and enhancing their efficacy while minimizing their side effects. Nanomaterials exhibit numerous benefits; however, their stability and toxicity pose potential risks to living organisms result in adverse effects, such as protein adsorption, and inflammation. Despite the challenges inherent to the development of nanomaterials, ongoing research and development have a great potential for the liver-targeted treatment of liver diseases through the use of nanotechnology. In this review, we first describe the nanomaterials used to target liver diseases, i.e., metallic NPs, ceramic nanomaterials, micelles, polysaccharides, liposomes, dendrimers, carbon nanotubes, and multifunctional NPs. Moreover, the mechanisms for nanomaterials target liver disease are discussed. Finally, this review discusses the current challenges and prospects for future research directions in this field.