BACKGROUNDGinkgo biloba seeds (GBS) are rich in flavonoids, proteins and reducing sugar, and have been consumed as food and medicinal nuts for thousands of years. However, the presence of ginkgotoxins and their poor palatability limit people's consumption of them.RESULTSThis study used solid‐state fermentation with Bacillus subtilis natto and Lactobacillus plantarum to enhance the safety and benefits of GBS. Optimized fermentation conditions increased the content of beneficial components like total flavonoids, soluble protein and reducing sugar while eliminating unpleasant odors (isoamyl aldehyde and hexanal) and reducing the toxin 4′‐O‐methylpyridoxine by 91.17%. Fermentation of GBS powder can significantly enhance its anti‐inflammatory and antioxidant activities in vitro (P < 0.001). Furthermore, it exhibits a dose‐dependent effect within a certain concentration range. Mixed fermentation (FBnLp) was evaluated for its effects on obesity and metabolic syndrome in mice fed a high‐fat diet. FBnLp significantly reduced body and liver weight gain, prevented dyslipidemia and decreased inflammatory and oxidative stress compared to unfermented GBS. Histological analysis showed that FBnLp improved liver health by reducing fat accumulation and preventing non‐alcoholic fatty liver disease. Meanwhile, it was found that feeding FBnLp increased the expression of CPT‐1α, which regulates energy expenditure and fat breakdown, and downregulated the expression of SREBP‐1c, FAS and ACC, which regulate fat synthesis.CONCLUSIONThis research provides new insights and technological support for the application and development of FBnLp as a functional product, addressing key issues in its use and industry growth. © 2024 Society of Chemical Industry.