Recently we have demonstrated that needle-like, cellulose-based nanomaterials, such as cationic derivatives of cellulose nanocrystals (CNCs, CNC-AEMA2) evoke immunological responses through NLRP3 inflammasome/IL-1β inflammatory pathway. We also previously demonstrated that curcumin, a naturally occurring polyphenolic compound isolated from Curcuma longa (Zingiberaceae), was able to suppress, at least in part, this immunological response, as observed by diminished IL-1β secretion in LPS/CNC-AEMA2-stimulated macrophages. These results are not a totally surprise because curcumin is a well-known antioxidant and antinflammatory natural compound. In addition to acting as “scavenger” of reactive oxygen species (ROS), several studies indicate that curcumin also upregulates antioxidant enzymes by activating the Nfr2 signaling pathway. However, the mechanisms by which this natural compound exerts its protective activity is still under investigation. We hypothesize that curcumin may also affect the redox status, such as S-glutathionylation, of key proteins involved in the NLRP3 inflammasome/IL-1β pathway, and therefore impacts their protein-protein interactions. The goal of this study was to investigate the effects of curcumin on the S-glutathionylation of NLRP3 induced by CNC-AEMA2 in LPS-primed mouse macrophages (J774A.1), as well as interactions among proteins of the NLRP3 inflammasome complex using immunoprecipitation and Western blot techniques. Cells were primed for 4h with lipopolysaccharide (LPS) in presence or absence of curcumin, and CNC-AEMA2 was added for another 20h. Our main finding indicates that the addition of curcumin concomitantly with LPS caused the greatest decrease in NLRP3 and increase in caspase-1 S-glutathionylation, which appears to favor protein-protein interactions in the NLRP3 complex. Taking together our results suggest that, at least in part, the antinflammatory activity of curcumin is associated with changes in S-glutathionylation of key NLRP3 inflammasome components, and perhaps resulting in sustained complex assembly and suppression of IL-1β secretion.