The interactions of He and Ne with propylene oxide have been investigated with the molecular beam technique by measuring the total (elastic + inelastic) integral cross section as a function of collision velocity. Starting from the analysis of these experimental data, potential energy surfaces, formulated as a function of the separation distance and orientation of propylene oxide with respect to the interacting partners, have been built: The average depth of potential wells (located at intermediate separation distances) has been characterized by analyzing the observed "glory" quantum effects, and the strength of long-range attractions has been obtained from the magnitude and the velocity dependence of the smooth component of measured cross sections. The surfaces, tested and improved against new ab initio calculations of minima interaction energies at the complete basis set level of theory, are defined in the full space of relative configurations. This represents a crucial condition to provide force fields useful to carry out, in general, important molecular property simulations and to evaluate, in the present case, the spectroscopic features and the dynamical selectivity of weakly bound complexes formed by propylene oxide, a prototype chiral species, during collisions in interstellar clouds and winds, in the space and planetary atmospheres. The adopted formulation of the interaction can be readily extended to similar systems, involving heavier noble gases or diatomic molecules (H2, O2, and N2) as well as to propylene oxide dimers.