It is still a challenge in studying the toughening mechanism by well combining the experimental and atomistic molecular dynamics (MD) simulation study. This article directly introduced eicosane (C20, model compound of paraffin) into the epoxy matrix (DGEBA) by using a special epoxy resin with alkyl side chains (D12) as a compatibilizer, which was synthesized through thiol-ene click chemistry. The toughening mechanism of the ternary DGEBA/D12/C20 (EPDA-X) systems was systematically investigated by experimental and MD simulation methods. Though C20 can be well dispersed in the curing mixture, the huge polarity difference between C20 and DGEBA can be the driving force for C20 to stay away from DGEBA, demonstrating the self-assembly effect of C20 around the alkyl side chains of D12 because of the good compatibility of D12 and C20. The soft alkyl chains of D12 and C20 as well as the self-assembly effect of C20 around the D12 molecules can simultaneously improve the strength, modulus, and toughness of the EPDA-2.5 system. This article not only provides a brand new toughening strategy by directly using nonfunctional alkyl derivatives as the toughening agent of epoxy composites with superior mechanical properties but also provides a systematic MD simulation method to evaluate whether there is the interaction or not and the strength of interaction between different molecular chains so as to provide a theoretical basis for the cause of the microphase separation structure and related toughening mechanism in cross-linking networks on the atomic and molecular levels.