A manufacturing method of a three-dimensional stretchable electronic device includes: preparing an aluminum mold for producing a substrate having one or more protrusions on an upper side and a lower side thereof; forming a path for a connection line for connecting the protrusions of the substrate using a wire; introducing a first polymer for forming the protrusions of the substrate into a predetermined portion of the aluminum mold; removing the wire and the three-dimensional stretchable substrate from the aluminum mold; injecting a liquid metal into the path for a connection line from which the wire was removed, thus manufacturing a three-dimensional stretchable substrate having a connection line; and transferring elements to the protrusions of the three-dimensional stretchable substrate having the connection line and connecting the elements to the connection line, thus connecting the elements to each other.