Background: While Toxoplasma gondii infection poses a significant health threat, its impact on the localized intestinal lipid metabolism remains unclear. Methods: Thus, this study established an acute infection model in BALB/cJ mice and analyzed the colonic contents collected 10 days post-infection via untargeted lipidomics. The lipid profiles of the two groups diverged substantially, with a clear separation evident between infection and control conditions. Results: We identified 65 upregulated and 87 downregulated differential lipids, primarily falling into the glycerophospholipids and sphingolipids categories. Pathway enrichment analysis revealed that the choline metabolism in cancer and glycerophospholipid metabolism pathways was pinpointed as being among the most perturbed following infection. Correlation and network analyses further suggested that key molecules, such as LPC (20:4) and LPA (18:0), may mediate these metabolic pathway abnormalities by regulating related enzymatic activities. Conclusions: This systematic characterization of the intestinal lipid metabolic landscape in mice during acute T. gondii infection revealed the host intestinal lipid metabolic reprogramming induced by T. gondii infection. The findings offer a novel metabolic perspective for understanding T. gondii pathogenesis and host–parasite interactions.