Wound healing is a major secondary complication in type 2 diabetes, which results in significant disability and mortality, imposing a significant clinical and social burden. Sustained activation of the Nod-like receptor protein (NLRP) inflammasome in wounds is responsible for excessive inflammatory responses and aggravates wound damage. The activation of the NLRP3 inflammasome is regulated by a two-step process: the priming/licensing (signal 1) step involved in transcription and posttranslation and the protein complex assembly (signal 2) step triggered by danger molecules. This review focuses on the advances made in understanding the pathophysiological mechanisms underlying wound healing in the diabetic microenvironment. Simultaneously, this review summarizes the molecular mechanisms of the main regulatory pathways associated with signal 1 and signal 2, which trigger the NLRP3 inflammasome complex assembly in the development of diabetic wounds (DW). Activation of the NLRP3 inflammasome-related pathway, involving the disturbance in Nrf2 and the NF-κB/NLRP3 inflammasome, TLR receptor-mediated activation of the NF-κB/NLRP3 inflammasome, and various stimuli inducing NLRP3 inflammasome assembly play a pivotal role in DW healing. Furthermore, therapeutics targeting the NLRP3 inflammasome-related pathways may promote angiogenesis, reprogram immune cells, and improve DW healing.