The two-volume set LNCS 16467-16468 constitutes the refereed proceedings of the 11th International Conference on Machine Learning, Optimization, and Data Science, LOD 2025, held in Castiglione della Pescaia, Italy, during September 21-24, 2025.The 58 full papers included in this book were carefully reviewed and selected from 180 submissions. They focus on machine learning, deep learning, AI, computational optimization, neuroscience and big data that includes invited talks, tutorial talks, special sessions, industrial tracks, demonstrations and oral and poster presentations of refereed papers.