The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in the kidney and the heart is increasingly being suggested to play a key role in mediating inflammation. In the kidney, NLRP3 activation was associated with the progression of diabetic kidney disease. In the heart, activation of the NLRP3 inflammasome was related to the enhanced release of interleukin-1β (IL-1β) and the subsequent induction of atherosclerosis and heart failure. Apart from their glucose-lowering effects, SGLT-2 inhibitors were documented to attenuate activation of the NLRP3, thus resulting in the constellation of an anti-inflammatory milieu. In this review, we focus on the interplay between SGLT-2 inhibitors and the inflammasome in the kidney, the heart and the neurons in the context of diabetes mellitus and its complications.