AbstractOrgan‐on‐a‐chip (OOC) devices bring innovative disease modeling and drug discovery approaches by providing biomimetic models of tissues and organs in vitro combined with biosensors. Miniaturized biosensor systems and tissue biofabrication techniques allow to create multiple tissues on a chip highly controlling the experimental variables for high‐content screening applications. In this work, a biomimetic multi‐OOC integrated platform composed of skeletal muscle and pancreatic cells is fabricated to study the impact of exercise on insulin secretion. Both engineered tissues are integrated with optical biosensing technology to monitor in real‐time the contraction‐induced myokine secretion and their effect on beta‐cells insulin production. Using this device, it is demonstrated that insulin secretion is induced directly by the effect of myotubes contractions. The cross‐talk platform would improve drug assays and provide a new model to study the loss of pancreas functionality associated with diabetes mellitus.