The exponential growth of biomedical literature necessitates advanced methods for Literature-Based Discovery (LBD) to uncover hidden, meaningful relationships and generate novel hypotheses. This research integrates Large Language Models (LLMs), particularly transformer-based models, to enhance LBD processes. Leveraging LLMs’ capabilities in natural language understanding, information extraction, and hypothesis generation, we propose a framework that improves the scalability and precision of traditional LBD methods. Our approach integrates LLMs with semantic enhancement tools, continuous learning, domain-specific fine-tuning, and robust data cleansing processes, enabling automated analysis of vast text and identification of subtle patterns. Empirical validations, including scenarios on the effects of garlic on blood pressure and nutritional supplements on health outcomes, demonstrate the effectiveness of our LLM-based LBD framework in generating testable hypotheses. This research advances LBD methodologies, fosters interdisciplinary research, and accelerates discovery in the biomedical domain. Additionally, we discuss the potential of LLMs in drug discovery, highlighting their ability to extract and present key information from the literature. Detailed comparisons with traditional methods, including Swanson’s ABC model, highlight our approach’s advantages. This comprehensive approach opens new avenues for knowledge discovery and has the potential to revolutionize research practices. Future work will refine LLM techniques, explore Retrieval-Augmented Generation (RAG), and expand the framework to other domains, with a focus on dehallucination.