This two-volume set LNBI 16050-16051 constitutes the proceedings of the 12th International Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2025, held in Canaria, Spain, during July 16–18, 2025. The 57 full papers presented in these volumes were carefully reviewed and selected from 98 submissions. They were organized into the following topical sections: Part I: Advances in Deep Learning in Bioinformatics and Bioengineering; Bioinformatics and Biomedical Applications; Biomarker Identification; Biomedical Computing; and Biomedical Engineering. Part II: Biosensors and Data Acquisition; Emerging Trends and Innovations in E-Health; High Performance in Bioinformatics; Innovations in Cancer Research: The Role of Bioinformatics and Biomedical Engineering; Machine Learning in Bioinformatics and Biomedicine; and Recent Advances in Bioinformatics.