Abstract: Objective To investigate the protective effect and mechanism of Polygonatum sibiricum polysaccharides (PSP) on diabetic cardiomyopathy (DCM). Methods Forty SPF-grade male Sprague-Dawley rats were divided randomly into Control, Model, PSP, and metformin groups. After 4 weeks of feeding a high-fat diet, streptozotocin was injected intraperitoneally to establish a rat model of diabetes mellitus. The drug was administered by gavage for 12 weeks, and body mass and blood glucose were recorded every 2 weeks. Cardiac function was detected by non-invasive echocardiography at week 16. Myocardial histopathological changes and the degree of myocardial fibrosis were assessed by hematoxylin and eosin and Masson staining. Serum interleukin (IL)-6, IL-1β, IL-18, tumor necrosis factor-α (TNF-α), triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein were detected by enzyme-linked immunosorbent assay. Expression levels of the fibrosis-related proteins transforming growth factor (TGF)-β1, Smad2, Collagen-Ⅰ, Collagen-Ⅲ, and the pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1 were detected in rat myocardial tissues by Western blot. Cellular experiments were performed by exposing H9c2 cells to high glucose (40 mmol/L) to mimic the in vitro DCM model, cell viability was detected by Cell Counting Kit-8 assay, and the apoptotic cell ratio was detected by flow cytometry. Results Rats in the treatment group had significantly lower blood glucose, lipid, and serum inflammatory factor levels compared with the model group (P<0.05), significantly higher ejection fraction and fractional shortening values (P<0.05), and improved cardiac function. Myocardial fibers were better aligned and collagen fiber accumulation was reduced, and myocardial tissue levels of NLRP3, ASC, Caspase-1, Collagen-Ⅰ, Collagen-Ⅲ, TGF-β1, and Smad2 were significantly reduced (P<0.05). In the cellular assay, PSP increased the viability and decreased the proportion of apoptotic cells in high glucose-induced H9c2 cardiomyocytes. Conclusions PSP can improve glucose-lipid metabolism, protect cardiac function, and delay the occurrence of myocardial fibrosis in diabetic rats, and can also improve the viability of cardiomyocytes. Its mechanism of action may be related to the inhibition of cellular pyroptosis and delayed occurrence of ventricular remodeling.