ScopeButyric acid (C4) and lauric acid (C12) are recognized as functional fatty acids, while the health benefits of the structural lipids they constitute remain unclear.Methods and resultsIn this study, lauric acid‐butyric structural lipid (SLBL) is synthesized through ultrasound‐assisted enzyme‐catalyzed acidolysis and its health benefits are evaluated in a high‐fat diet‐induced obesity mouse model. SLBL and its physical mixture (MLBL) do not significantly inhibit obesity in mice. However, SLBL treatment increases the ratio of n3/n6 fatty acids in the liver and improves obesity‐induced hepatic lipid metabolism disorders. Furthermore, the expression of liver pro‐inflammatory cytokines (interleukin [IL]‐6, IL‐1β, TNF‐α) are significantly suppressed by SLBL, while the expression of anti‐inflammatory cytokine (IL‐10) is increased. Moreover, SLBL ameliorates the dysbiosis of small intestinal microbes induced by high‐fat diet and regulates microbial community structure to be close to the control group. Especially, SLBL significantly alleviates the high‐fat diet‐induced decrease in Dubosiella and Bifidobacterium abundance. Correlation analysis reveals that SLBL treatment increases the abundance of microorganisms with potential anti‐inflammatory function and decreases the abundance of potentially pathogenic bacteria.ConclusionIn all, small intestinal microbes may be a significant bridge for the positive anti‐inflammatory effects of SLBL, while the exact mechanism remains to be clarified.