The design and fabrication of miniaturized, implantable, low-power wireless systems for continuous glucose monitoring hold great promise for diabetes mellitus inflicted patients. This involves addressing a variety of issues including extreme circuit miniaturization, robust electrochemical sensors as well as counteracting negative tissue response and biofouling following sensor implantation. In this contribution, we present a highly miniaturized microelectronic sensor platform that fits through a hypodermic needle and holistically addresses all aforementioned tribulations. For this, a custom designed complementary metal-oxide-semiconductor electronic device employing the 0.35 µm design rule has been integrated with a high performance amperometric electrochemical glucose sensor. The fabricated electrochemical sensor utilizes the stratification of five functional layers resulting in linear amperometric response within the physiological glucose range (2 -22 mM). The sensor is encased with a thick polyvinyl alcohol (PVA) hydrogel containing poly (lacticco-glycolic acid) (PLGA) microspheres which provides continuous, localized delivery of dexamethasone utilized to combat inflammation and fibrosis subsequent to implantation. In vivo evaluation in a rat has shown that this system accurately tracks glycemic events. Such miniature size and low power operation (0.665 mm 2 and 140 µW, respectively) of the electronic system render it an ideal platform for continuous glucose monitoring and other metabolic sensing applications.