This study is aimed to explore the regulatory effect and mechanism of Jingfang Mixture (JF) on thrombosis rats through the gut-liver axis through a carrageenan-induced rat model. The results showed that after JF treatment, the pathological condition of the tail was improved, the four coagulation parameters and the levels of coagulation factors were adjusted closely to the normal levels, and the levels of liver and intestinal inflammatory factors were significantly reduced. In vitro experiments proved JF had little effect on platelet aggregation, release, and coagulation. In our study, JF can significantly improve intestinal flora disorders, alleviate the oxidative stress level in the liver, and improve the short-chain fatty acid levels in the feces of rats with thrombosis. Of note, the relative abundances of Clostridia_UCG-014, Ruminococcaceae were significantly decreased after JFM intervention. Proteomic results showed that JF may be related to the coagulation and complement cascade signaling pathway. Finally, we further confirmed the therapeutic effect through FMT experiments, that the crosstalk of the gut-liver axis contributed to the improvement of thrombosis after JF treatment. In summary, this study took the gut-liver axis as the breakthrough point and coupled with 16S rDNA sequencing, non-targeted metabolomics, TMT-based quantitative proteomics and related comprehensive analysis methods, showing that JF can improve the intestinal flora and immune system disorder, as well as reduce the inflammatory damage of intestinal and liver in carrageenan-induced thrombosis rats, and its protective effect may be related to the complement and coagulation cascade signaling pathway.