BACKGROUNDKiwifruit pomace, which contains abundant phenolic compounds, is typically discarded during the juicing process, leading to wastage of valuable resources. To address this issue, various indicators (including total acidity, sugar/acid ratio, vitamin C, total polyphenols, polyphenol monomers, and soluble solids content) of 15 kiwifruit cultivars were evaluated and juiced. Then, a polyphenol‐concentrated solution from kiwifruit pomace was backfilled into kiwi juice to prepare whole nutritious compound kiwi juice, and its anti‐hyperlipidemic activity on obese model mice was then investigated.RESULTSThrough grey relational analysis and the technique for order preference by similarity to an ideal solution (TOPSIS), Kuimi and Huayou were identified as the predominant varieties for juicing, with weighted relevance scores of 0.695 and 0.871 respectively and TOPSIS scores of 0.6509 and 0.8220 respectively. The polyphenol content of Cuixiang pomace was 43.97 mg g−1, making it the most suitable choice for polyphenol extraction. By backfilling a polyphenol‐concentrated solution derived from Cuixiang pomace into compound kiwi juice of Huayou and Kuimi, the whole nutritious compound kiwi juice with polyphenols was produced and exhibited superior bioactivities, including enhanced hepatic oxidative stress defense, and alleviated serum lipid abnormalities. Furthermore, whole nutritious compound kiwi juice with polyphenols ameliorated host intestinal microbiota dysbiosis by increasing the relative abundance of the phyla Bacteroidota and Verrucomicrobiota.CONCLUSIONA hypolipidemic dietary supplement based on kiwifruit pomace polyphenols has been successfully developed, providing an effective solution for hyperlipidemia intervention. © 2023 Society of Chemical Industry.