Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing 3 (NLRP3) is a signaling pathway that is involved in inflammatory cascades, cell survival and the immune response. NLRP3 is activated by cellular damage, oxidative stress, and other factors that stimulate the immune system. Stimulation of NLRP3 induces inflammatory reactions and the production of inflammatory cytokines. These inflammatory mediators are implicated in several diseases. Metformin (MET) is an anti-hyperglycemia agent that is extensively used in clinical practice worldwide due to its high efficiency, safety profile, and affordable price. MET is the only member of biguanide class that is used in clinical practice and a potent AMP-activated protein kinase (AMPK) agonist with proven anti-inflammatory characteristics. Due to its anti-inflammatory properties, MET is considered to be effective against diseases that have an inflammatory background, and the NLRP3 pathway is involved in the pathophysiology of these disorders. In this review, we have evaluated the evidence if MET can affect this pathway and its utility for future therapeutic approaches.