Pyroptosis is identified as a pro-inflammatory programmed cell death, mediated by gasdermins (GSDMs) family of proteins accompanied by pro-inflammatory signals release. As essential players in innate immunity, inflammasomes are intracellular protein complexes which cleave gasdermin D (GSDMD), forming structurally stable pores in the cell membrane, subsequently inducing pyroptosis. Extensive evidence indicates that inflammasomes and pyroptosis contributes to tumors, nerve injury, inflammatory diseases and metabolic disorders. As a metabolic disorder, diabetes is characterized with hyperglycemia, insulin resistance and chronic inflammation. Meanwhile, aberrant pyroptosis exerts a key role in the occurrence and progression of diabetes and its common complication, diabetic nephropathy (DN). Furthermore, evidence has shown that DN patients and animal models exhibit increased circulating IL-1β and inflammasome, while decreasing the expression of key components of the inflammasome mitigates kidney damage and delays progression. Current research has reported that non-coding RNAs (ncRNAs) are involved in activation of inflammasomes and play a crucial role in the control of pyroptosis in DN pathogenesis. In addition, studies have indicated that some natural plant compounds have therapeutic potential via regulation of inflammasomes and pyroptosis to prevent and potentially treat DN. This mini-review examines the molecular mechanism of inflammasome activation and pyroptosis, highlights the critical roles of ncRNA and explores potential therapeutics to regulate pyroptosis in DN.