High-grade serous ovarian cancer (HGSOC) is a preferential omental metastasis malignancy. Since omental adipose tissue is an endocrine organ, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to compare the peptides secreted from omental adipose tissues of HGSOC and benign serous ovarian cysts (BSOC). Among the differentially secreted peptides, we detected 58 upregulated peptides, 197 downregulated peptides, 24 peptides that were only in the HGSOC group and 20 peptides that were only in the BSOC group (absolute fold change ≥ 2 and <i>P</i> < 0.05). Then, the basic characteristics of the differential peptides were analyzed, such as lengths, molecular weights, isoelectric points, and cleavage sites. Furthermore, we summarized the possible functions according to the precursor protein functions of the differentially expressed peptides by Gene Ontology (GO) analysis with the Annotation, Visualization, and Integrated Discovery (DAVID) database and canonical pathway analysis with IPA. For the GO analysis, the differentially secreted peptides were mainly associated with binding in molecular function and cellular processes in biology process. For the canonical pathways, the differentially secreted peptides were related to calcium signaling, protein kinase A signaling, and integrin-linked kinase (ILK) signaling. We also identified 67 differentially secreted peptides that located in the functional domains of the precursor proteins. These functional domains were mainly related to energy metabolism and immunoregulation. Our study might provide drugs that could potentially treat HGSOC or omental metastases of HGSOC cells.