With Smart Drug Delivery Technology, the unprecedented progress of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. To enhance their therapeutic effects and reduce the related side effects, active drug molecules should selectively accumulate in the disease area for a prolonged period with high controllability. Drug delivery refers to the approaches, formulations, technologies, and systems for transporting therapeutics in the body as needed to safely and efficiently achieve their desired therapeutic effects. Conventional drug delivery systems (DDSs) are often accompanied by systemic side effects that mainly attributable to their nonspecific bio-distribution and uncontrollable drug release characteristics. To overcome these limitations, advanced controlled DDSs have been developed to achieve the release of payloads at the target sites in a spatially controlled manner. In comparison to the conventional DDSs, the smart controlled DDSs can effectively reduce the dosage frequency, while maintaining the drug concentration in targeted organs/tissues for a longer period of time. In this sense, the controlled DDSs provide broad insights and fascinating properties for decreasing drug concentration fluctuation, reducing drug toxicities and improving therapeutic efficacy.