This study investigated the effect of Corydalis saxicola Bunting total alkaloids (CSBTA) on pyroptosis in macrophages (Mϕ). In the Mϕ pyroptosis model, an inverted fluorescence microscope was used to assess cell pyroptosis, while a scanning electron microscope was used to observe morphological changes in Mϕ. NLR family pyrin domain‐containing 3 (NLRP3), caspase‐1, and gasdermin D (GSDMD) expression levels were detected by polymerase chain reaction and western blotting, whereas interleukin‐1 (IL‐1) and interleukin‐18 (IL‐18) expression levels were measured by an enzyme‐linked immunosorbent assay. After pretreatment with CSBTA or the caspase‐1 inhibitor, acetyl‐tyrosyl‐valyl‐alanyl‐aspartyl‐chloromethylketone (Ac‐YVAD‐cmk), it was discovered that NLRP3, caspase‐1, and GSDMD expressions were significantly reduced at both the mRNA and protein levels, as were IL‐1 and IL‐18 levels. The inhibitory effects of CSBTA and Ac‐YVAD‐cmk did not differ significantly. These findings indicate that CSBTA blocks Porphyromonas gingivalis‐lipopolysaccharide‐induced Mϕ pyroptosis.