This review explores the advancements in biosensor technology, focusing on the use of macrocyclic and macromolecular conjugated systems, such as phthalocyanines, porphyrins, and polymers, in the development of hybrid composite materials. These materials are designed to enhance the sensitivity, selectivity, thermal stability, mechanical flexibility, biocompatibility, and tunable electrical properties of biosensors. The review covers synthetic strategies, properties, working mechanisms, and the potential of these systems for detecting various biomolecules, including glucose, hydrogen peroxide, uric acid, ascorbic acid, dopamine, cholesterol, amino acids, and cancer cells. It also discusses the challenges and future directions in the field, emphasizing the importance of smart design and material enhancement in improving biosensor performance across various applications. The review highlights the role of macrocycle-based hybrid composites in overcoming limitations of single-element biosensors and enhancing their effectiveness in detecting biomolecules.This review explores the advancements in biosensor technology, focusing on the use of macrocyclic and macromolecular conjugated systems, such as phthalocyanines, porphyrins, and polymers, in the development of hybrid composite materials. These materials are designed to enhance the sensitivity, selectivity, thermal stability, mechanical flexibility, biocompatibility, and tunable electrical properties of biosensors. The review covers synthetic strategies, properties, working mechanisms, and the potential of these systems for detecting various biomolecules, including glucose, hydrogen peroxide, uric acid, ascorbic acid, dopamine, cholesterol, amino acids, and cancer cells. It also discusses the challenges and future directions in the field, emphasizing the importance of smart design and material enhancement in improving biosensor performance across various applications. The review highlights the role of macrocycle-based hybrid composites in overcoming limitations of single-element biosensors and enhancing their effectiveness in detecting biomolecules.