The fermentation process of Platycodon grandiflorus was optimized to enhance polysaccharide yield and the protective effect of the fermentation products on LPS-induced pneumonia-related cardiac injury in mice was investigated. Lactobacillus plantarum xdx-6801 and Pediococcus pentosaceus ZY-23 were cocultured in a 1:1 ratio. The appropriate ranges of fermentation parameters were determined using single-factor experiments, and the fermentation conditions were optimized using an orthogonal experiment. The protective effect of optimized P. grandiflorus fermentation liquid (FPG) on LPS-induced acute lung injury (ALI) and cardiac damage in C57BL/6J mice was verified through in-vivo experiments. The optimal fermentation conditions were 4% inoculum, temperature of 38 ℃, and duration of 60 h. Under these conditions, the polysaccharide content in FPG reached 237.48 μg•mL–1, and the total saponin content was 222.39 μg•mL–1. These values were 2.54 times and 1.02 times higher, respectively, than those in unfermented samples. FPG effectively alleviated lung and cardiac injury in LPS-induced ALI model mice, reduced the expression of the inflammatory factors interleukin 6 (72.30%), interleukin 1β (54.66%), and tumor necrosis factor alpha (53.44%), increased the activity of the antioxidant enzymes glutathione (28.01%) and superoxide dismutase (44.35%), as well as total antioxidant capacity (37.81%), and suppressed the accumulation of oxidative damage marker malondialdehyde (53.25%). Furthermore, FPG significantly improved cardiac pumping function in ALI mice, increasing the ejection fraction (44.50%) and fractional shortening (79.48%), while markedly reducing the level of the cardiac injury marker cardiac troponin I (65.95%). In conclusion, the optimized fermentation process significantly increases the polysaccharide content of P. grandiflorus, and the fermentation product exerts a marked protective effect against pneumonia-related cardiac injury, providing a theoretical basis for the application of P. grandiflorus in the prevention and treatment of pneumonia and its complications.