Motivated by the rich phase behavior and diverse functionalities of amphiphilic and polyphilic molecules consisting of at least two mutually incompatible segments, we use molecular simulations with multiscale modeling to study the self-assembly of some representative molecules and their performance for the Li-ion transport. For a large family of bolapolyphiles typically composed of a rod-like π-conjugated core tethered with glycerol groups at both ends and with flexible non-polar chains at lateral positions, a simple coarse-grained (CG) model is adopted to form a wide range of ordered structures, some of which exhibit intriguing three-dimensional periodicity related to primitive, diamond and gyroid networks. Based on the obtained phase diagram from our simulations, some molecular design strategies are summarized regarding the segmental composition, the lateral chain shape and the attachment between core and lateral chain. To comply with the study of Li-ion transport, a chemistry-specific CG model is developed for polyphilic molecules, whose constituent segments include oligothiophene, oligo(ethylene oxide) and n–alkane, denoted as “T”, “EO” and “C”, respectively. The CG force field is parameterized using an atomistic model and experimental liquid density data. To characterize the assembled ordered structures, X-ray diffraction analysis assisted by molecular simulations makes a significant contribution in the case of bolapolyphiles to verify the periodic order and obtain the unit cell information, and in the case of a linear amphiphile, BTTT/dEO4, to determine its thin film structure and track the film expansion upon the Li-salt addition. At last, the Li-ion transport is investigated using an atomistic model in a series of T-shaped polyphilic molecules, 5T/dC6/EOn, where a detailed examination on the Li-ion solvation environment provides some mechanistic insights of the Li-ion hopping event.