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The gating or capping of pores of mesoporous silica nanoparticles (MSNPs) via stimuli-responsive molecules or moieties has effective therapeutic outcomes against life-threatening diseases such as diabetes and cancer. Most of the research in this field has shown the moral controlled drug delivery characteristics of the MSNPs, both in vitro and in vivo. Numerous internal (like pH, enzyme, glucose, redox, etc.) and external (like temperature, light etc.) stimuli were used with diverse kinds of stimuli-responsive molecules for the controlled release of drugs, proteins, RNA, etc. from MSNPs. The MSNPs-based delivery platforms have minimal side effects, with the least premature drug leakage and augmented site-specific cargo delivery ability. These intelligent drug delivery systems have shown remarkable potential against many diseases, especially cancer. This chapter discusses various strategies utilized via the …