For insulin delivery, many reported glucose-sensitive materials are designed to response to the glucose in the blood. However, few particular studies on their blood compatibility have been reported. In this article, for controlled insulin release in diabetes therapy, a glucose-sensitive nanogel was prepared through thermally initiated precipitation polymerization using the aminophenylboronic acid-containing monomer to copolymerize with methacrylic acid. The obtained nanogels showed the uniform and spheroidal morphology as observed by SEM, and their sizes in aqueous solution are dependent on the concentration of glucose. Through in vitro and in vivo insulin release tests, it was found that nanogels showed the glucose-dependent insulin release and prolonged effect of lowing blood glucose level. The blood compatibility of nanogels has also been explored through various assays including the hemolysis, activated partial thromboplastin time, prothrombin time as well as the thromboelastography. All results indicated that the obtained glucose-sensitive nanogels showed good blood safety. Moreover, their low cytotoxicity suggested a potential application in diabetes therapy.