In recent years, there has been an escalating interest in stimuli-responsive drug delivery systems (SRDDS) due to their ability to revolutionize the delivery of therapeutics. SRDDSs offer a multitude of benefits in comparison to conventional drug delivery systems (DDS), including spatiotemporal control of drug release, targeted delivery, and improved therapeutic efficacy. The development of various classes of stimuli-responsive DDS, such as pH-responsive, temperature-responsive, photo-responsive, redox responsive systems, has been propelled by advances in materials science, nanotechnology, and biotechnology. These systems exploit specific environmental or physiological cues to trigger drug release in a precisely controlled manner, making them highly promising for the treatment of various diseases. In this review article, an in-depth exploration of the principles, mechanisms, and applications of SRDDS in the context of diverse pathologies such as cancer, arthritis, Alzheimer’s disease, atherosclerosis and tissue engineering has been provided. Furthermore, this article delves into the discussion of recent patents, market overview and the progress of research in clinical trials. Overall, this article underscores the transformative potential of SRDDS in enabling personalized, precise, and effective drug delivery for the treatment of the above-mentioned diseases.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.