The combination of Quantum Mechanics (QM) and Molecular Mechanics (MM) methods has become an alternative tool for many applications for which pure QM and MM are not suitable. The QM/MM method has been used for different types of problems, for example: structural biology, surface phenomena, and liquid phase. In this paper we have used this method on the molecular structure of ipolamiide. The equilibrium geometry, harmonic vibrational frequencies and Raman activities were calculated byQM/MMmethodwithB3LYP/6-31G(d,p) and universal force field (UFF) combination usingONIOMcode.We found the geometry obtained by the QM/MM method to be very accurate, and we can use this rapid method in place of time consuming ab initio methods for large molecules. A detailed interpretation of the Raman spectra of ipolamiide is reported. The scaled theoretical wave numbers are in perfect agreement with the experimental values. The FT-Raman spectra of ipolamiide has been taken fromthe literatures.