Abstract: Drosophila melanogaster is one of the ideal models for evaluating the activity of natural products. In this study, a dextran sulfate sodium (SDS)-induced intestinal inflammation model in Drosophila is established to investigate the ameliorative effects on intestinal inflammation of guava extracts obtained by different methods (traditional water extraction and alcohol precipitation versus a complex enzymatic hydrolysis-assisted deep eutectic solvent method) as well as of different fractions after separation and purification. The results show that the guava polysaccharides extracted by the complex enzymatic hydrolysis-assisted deep eutectic solvent method significantly increases the survival rate of SDS-treated flies and reduces the intestinal barrier permeability. After further separation and purification, the GPB-1 fraction outperformes the GPA fraction in prolonging lifespan, reducing intestinal barrier permeability, restoring gut length and enhancing antioxidant capacity. A comprehensive evaluation system for natural product activity is established using Drosophila as a model, covering the entire workflow from polysaccharide extraction, separation, purification to activity evaluation. It integrates multidisciplinary knowledge from biological science, food nutrition, food chemistry and instrumental analysis. This system not only helps students master natural product extraction techniques, activity evaluation methods and data analysis, but also provides a low-cost and ethically friendly platform for hands-on training, thereby promoting students’ knowledge transfer and comprehensive skill improvement.