Spurred by recent advances in materials chemistry, molecular pharmaceutics and nanobiotechnology, stimuli-responsive “smart” systems offer opportunities for precisely delivering drugs in dose-, spatial- and temporal-controlled manners. In this talk, I will discuss our ongoing efforts in developing physiological signal-triggered bioinspired drug delivery systems. I will first present the glucose-responsive synthetic systems for biomimetic delivery of insulin for diabetes treatment. Bioresponsive microneedle patches and vesicle fusion-mediated synthetic beta cells will be emphasized. I will further discuss the local and targeted delivery of immunomodulatory therapeutics for enhanced cancer therapy. Our latest study utilizing platelets, cell conjugates and gels for delivery of immune checkpoint inhibitors will be specifically introduced.