Background <p>Gallbladder cancer (GBC) is associated with a poor prognosis due to the challenges in early diagnosis. The gallbladder’s anatomical constraints make it difficult to obtain tumor tissue for histological analysis and diagnostic monitoring. Consequently, liquid biopsy (LB) has emerged as a vital technique for minimally invasive extraction of tumor-derived materials. This review explores various non-invasive methods for GBC screening, with a particular focus on liquid biopsy.</p> Methods <p>A comprehensive search was conducted on PubMed, Scopus, Web of Science, and Google Scholar for articles published from 1994 to 2025. The key search terms were “Gallbladder cancer”, Liquid biopsy” “cfDNA”, “ctDNA”, “CTCs”, “Exosomes” and “Clinical trial”. Relevant articles on the subsections were included in this narrative literature review.</p> Conclusion <p>Liquid biopsy, one of the most promising and innovative diagnostic tools, was analyzed in detail, including its application in clinical studies for GBC. Despite its challenges, and varied results, this method shows potential for early GBC detection and treatment. Tissue specimens often fail to capture the dynamic evolution of cancer genomes and the genetic heterogeneity of metastatic cancers, while liquid biopsies, being more sensitive than cytology, can enhance the diagnosis and monitoring of GBC at various stages. This approach, thus, harbors the potential to facilitate cancer genetic profiling, paving the way for precision oncology strategies.</p> Graphical Abstract <p></p>