A periodic density functional theory study of the isomerization reactions of alkylated benzothiophene derivatives (i.e., dimethylated and monomethylated dibenzothiophenes and monomethylated benzotiophenes) catalyzed by acidic mordenite zeolite is reported. Monomolecular isomerization reactions have been considered and analyzed. The different reaction pathways are discussed in detail. The use of periodic structure calculations takes into consideration the electrostatic contributions and steric constraints that occur within the zeolite micropore. The isomerization reactions have been regarded as being helpful in hydrodesulfurization reactions of alkylated benzothiophene derivatives catalyzed by solid acid-metallic sulfide bifunctional catalysts.