Controlled drug release systems can ameliorate the release, absorption, metabolism and excretion of drug molecules in the body, significantly improve drug utilization and reduce the side effects of drugs. Intelligent-responsive hydrogels have been extensively studied for controlled drug release carriers due to their responsiveness, hydrophilicity, good biocompatibility and non-toxicity. In this paper, the research progress of the intelligent-responsive hydrogels-based controlled drug release systems is summarized in detail, including the conception, mechanism and applications. According to the kinds of external stimuli, the intelligent-responsive hydrogels-based controlled drug release systems can be classified into pH-responsive, temperature-responsive, light-responsive, glucose-responsive, enzyme-responsive, electric field-responsive, magnetic field-responsive, pressure-responsive, redox-responsive and multiple-responsive hydrogels-based controlled drug release systems. The applications of the intelligent-responsive hydrogels-based controlled drug release systems in treating diseases, such as cancer, acute kidney injury, eye diseases, diabetes and its complications, and antibiotic treatments for preventing wound infection are further briefly described. Then, the problems of the intelligent-responsive hydrogels-based controlled drug release systems researches, such as poor biocompatibility, burst release or stagnant release, and non-degradability, are analyzed. Finally, the future development of the intelligent-responsive hydrogel-based controlled drug release systems is prospected.