The ever-growing biomedical publications magnify the challenge of extracting structured data from unstructured texts. This task involves two components: biomedical entity identification (Named Entity Recognition, NER) and their interrelation determination (Relation Extraction, RE). However, existing methods often neglect unique features of the biomedical literature, such as ambiguous entities, nested proper nouns, and overlapping relation triplets, and underutilize prior knowledge, leading to an intolerable performance decline in the biomedical domain, especially with limited annotated training data. In this paper, we propose the Biomedical Relation-First eXtraction (Bio-RFX) model by leveraging sentence-level relation classification before entity extraction to tackle entity ambiguity. Moreover, we exploit structural constraints between entities and relations to guide the model’s hypothesis space, enhancing extraction performance across different training scenarios. Comprehensive experimental results on biomedical datasets show that Bio-RFX achieves significant improvements on both NER and RE tasks. Even under the low-resource training scenarios, it outperforms all baselines in NER and has highly competitive performance compared to the state-of-the-art fine-tuned baselines in RE.