Objective To investigate the molecular mechanism of Sansheng Hehuan Yin in treating lipid metabolism-related depression based on network pharmacology. Methods Target genes of Sansheng Hehuan Yin and those related to lipid metabolism-related depression were screened from databases. A “Chinese herbal compound-active ingredient-key target” network and a protein-protein interaction network were constructed, followed by GO and KEGG enrichment analyses. Results A total of 911 target genes of Sansheng Hehuan Yin and 9,017 disease-related target genes were identified, yielding 724 overlapping targets. Twenty-one core genes, including PTGS2, HSP90AA1, and ESR1, were screened from the PPI network. A total of 11,307 GO entries were enriched, involving biological processes such as protein phosphorylation and cellular response to lipid, cellular components such as membrane raft and dendrite, and molecular functions such as protein kinase activity. KEGG enrichment analysis identified 313 signaling pathways, including pathways in cancer, lipid and atherosclerosis, among others. Conclusion Sansheng Hehuan Yin may exert its therapeutic effects on lipid metabolism-related depression through multiple targets, components, and signaling pathways.