The enrichment of peptides is a key technique in mass spectrometry based proteomics and peptidomics. The tailored design of mesoporous materials with an optimum pore size for highly-efficient enrichment of target molecules is a challenging issue. Herein, a series of periodic mesoporous organosilicas (PMOs) are synthesized with the same structural symmetry (p6mm) and similar morphology, while the pore sizes are finely adjusted from 2.6 to 7.3 nm. Their enrichment performance for a standard E7 peptide (molecular weight 1120.6 Da) is investigated via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). It is found that PMO with the mesopore size of 5.8 nm exhibits the highest enrichment performance towards the E7 peptide. Moreover, a block copolymer (Brij 78) with the similar molecular weight (1150.8 Da) to E7 is also used to further study the influence of mesopore size upon the enrichment efficiency. It is shown that PMO with the pore size of 5.8 nm still holds the best enriching ability towards Brij 78 at low concentrations. The adsorption capacity of the PMOs for Brij 78 are further studied at high concentrations, showing a dependence on both the pore volume and pore size. This research may shed light on advanced enrichment and analysis of various peptides and polymers using designed nanoporous materials, an important topic in both material and biological science.