ScopePeriodontitis is one of the most prevalent chronic inflammatory diseases with impaired autophagy. Agaricus blazei Murrill polysaccharide (ABMP) shows beneficial effects in various inflammatory diseases. However, whether ABMP is involved in autophagy regulation and periodontitis attenuation remains to be elucidated.Methods and resultsThis study firstly shows the dynamic changes in inflammatory and autophagy levels in silk ligature periodontitis model. Then the positive regulation effect of autophagy on inflammation and its vital role in ABMP inhibiting PDLCs inflammatory response are testified in LPS‐treated PDLCs. Secondly, the Micro‐CT, quantitative RT‐PCR, Western Blot, TRAP, and immunofluorescence staining analysis are performed to assess the effects of ABMP on periodontitis and autophagy. The data show the augmented autophagy and alleviated gingival recession, inflammatory cell infiltration, alveolar bone resorption, and reduced osteoclasts in periodontitis by ABMP treatment. Further experiments using chemical inhibitors demonstrate the vital role of H2S/NRF2 axis in ABMP‐induced appropriate level of autophagy augmentation against periodontitis.ConclusionsCollectively, the findings not only reveal the unrecognized capacity and mechanism of ABMP as an effective and potential dietary intake against periodontitis, but also suggest the possibility for ABMP to be used in the treatment of other autophagy‐related diseases.