Naturally forming benzoic acid in fermented dairy products accumulates in organisms and biomagnifies through collateral transport. The association between benzoic acid agglomeration and susceptible lipid nutrients remains obscure. Horizontal analysis of lipidomic alteration in response to benzoic acid was conducted and the spatially proteomic map was constructed using label-free quantitative proteomics. From synergistic integration of multi-omics in benzoic acid accumulated fermented goat milk model, the biological processes of significant proteins mostly focused on glyceride-type polyunsaturated fatty acids degradation (143.818 ± 0.51 mg/kg to 104.613 ± 0.29 mg/kg). As a physiological barrier shield, perilipin, which is coated on the surface of lipid droplets, protects triacylglycerols from cytosolic lipases, thus preventing triglyceride hydrolysis. The expression of perilipin decreased by 90% compared with the control group, leading to the decrease of triglycerides. Benzoic acid suppressed phosphatidylethanolamines and phosphatidylcholines synthesis by attenuating choline phosphotransferase and ethanolamine phosphotransferase. Less diglyceride generated by the dephosphorylation of phosphatidic acid entered choline phosphotransferase and ethanolamine phosphotransferase-mediated glycerophospholipid metabolisms. Fermentation of goat milk at a low temperature and less incubation time leads to the production of less benzoic acid and mitigation of lipid nutrient loss. The present study delineated the molecular landscape of fermented goat milk containing endogenous benzoic acid and further dissected the trajectory guiding lipid alteration to advance control of benzoic acid residue.