Background: Endometritis is a common gynecological disease characterized by inflammation of the endometrium. The gynecological Tiaoqi Jiedu formula has been widely used to treat endometritis with dampness and heat. However, the mechanism of action remains unclear. Methods: A mouse model of endometritis with dampness and heat was established. The pathological changes of the uterus and tongue were detected by hematoxylin and eosin (HE) staining. Gastric aquaporin 3 (AQP3) and uterine cluster of differentiation 14 (CD14) protein were detected by immunohistochemistry. Concentrations of serum inflammatory factors interleukin-6 (IL-6), IL-1\beta, tumor necrosis factor \alpha (TNF-\alpha), IL-10, and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expressions of nucleotide binding oligomerization domain- (NOD-), leucine-rich repeat- (LRR-) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3), gasdermin D (GSDMD), caspase-1, toll-like receptor 4 (TLR4), p65, and phosphorylation of p65 (p-p65) were determined by real-time polymerase chain reaction (PCR) and Western Blot, respectively. Results: In the mouse model of endometritis, the medium- and high-doses of Tiaoqi Jiedu formula, and western medicine significantly downregulated the inflammatory factors IL-6, IL-1\beta, TNF-\alpha, and IL-8. It upregulated the anti-inflammatory factor IL-10, and inhibited pyroptosis and the expression of key proteins in the TLR4/nuclear factor-\kappaB (NF-\kappaB) signaling pathway. Conclusions: The Tiaoqi Jiedu formula demonstrated anti-inflammatory, anti-pyroptosis, and protective effects in endometritis. It has the potential to be a therapeutic option for the treatment of endometritis.