The investigation of geographical feed raw materials is crucial to maintain the sustainable development of aquaculture. Ensuring the intestinal health of aquatic animals is the key to improving the absorption and utilization rate of new protein sources. In the present study, a composite protein source derived from the sargassum enzyme-hydrolysate compound fish protein hydrolysate ("SFPH" in the experiment) was utilized to replace 0 %, 5 %, 10 %, 20 %, 30 %, and 40 % of fish meal protein, respectively. Pacific white shrimp (Penaeus vannamei) with an initial weight of 0.9 g was used as experimental model for an 8-week feeding trial. The results revealed that SFPH replacement reduced the width of intestinal microvilli, but the 5%SFPH group significantly increased intestinal wall thickness and microvilli height. Antioxidant indicators analysis revealed that when over 10 % of fish meal protein was substituted with SFPH, the total antioxidant capacity dramatically decreased. When SFPH replaced 40 % of fish meal protein, the mRNA expression levels of endoplasmic reticulum stress-related indicators (bip and atf4) significantly increased, as well as the genes associated with apoptosis (jnk, caspase 8 and caspase 3). The analysis of intestinal microbiota showed that the 5%SFPH group significantly increased the richness of intestinal microbiota and significantly increased the abundance of beneficial bacteria (Campilobacter, Patescibacter, Deferribacter and Halobacter). The 40%SFPH group significantly increased the abundance of pathogenic bacteria (Pseudomonas, Serratia, Rickettsia, Edwardsiella, and Veillonella). A total of 201 differential relative abundance metabolites were detected by metabolomics, among which the contents of succinate, oxidized glutathione and reduced glutathione were reduced in the 40%SFPH group. The differential metabolites were mainly enriched in cysteine and methionine metabolism, biosynthesis of amino acid and glutathione metabolism. Based on the integrated analysis of metabolomics and intestinal microbiota, changes in signal pathways such as amino acid metabolism and glutathione synthesis may be the main reasons for the high proportion of SFPH disrupting intestinal health. This study provides in-depth data on the reaction mechanisms of shrimp to seaweed protein, and also provides new directions for the improvement of seaweed protein in the future.