To realize high-performance and intrinsically stretchable materials for field-effect transistor (FET) devices, a plethora of approaches about structure design have been explored. Herein, we report a new approach to control the carrier mobility-stretchability properties of the polymers by tuning the hydrophilicity and asymmetric side-chain combination. A series of isoindigo- bithiophene (II2T)-based semiconducting polymers with three kinds of side chains including carbosilane side chain, semifluorinated side chain, and oligoether side chain were synthesized for investigating the structure-mobility and structure-stretchability relationships. The experimental results showed that the molecular stacking pattern and orientation of the derived polymers could be controlled by altering the hydrophilicity and asymmetric side-chain combination. The side chains of carbosilane and oligoether and a semifluorinated side chain could provide an order edge-on stacking, conformability and backbone aggregation, and an irregular solid-state aggregation, respectively. Among them, P(Si-O) with oligoether and a carbosilane side chain exhibited an enhanced mu(h) of 0.56 cm(2) V-1 s(-1), edge-on stacking, and aggregation behavior owing to the favorable intermolecular interaction between the oligoether side chain and the asymmetric side chain to mitigate the steric hindrance. Also, P(Si-O) possessed a remarkable stretchability of (92%,(perpendicular to), 82%,(parallel to)) orthogonal mu(h) retention under 100% strain and almost unchanged mu(h) was observed after 1000 stretching-releasing cycles at 60% strain. The experimental results suggested that the combination and hydrophilicity of side chain played a pivotal role in developing semiconducting polymers with a high performance and an intrinsic stretchability.