Abstract Background Obesity is one of the major public health problems worldwide, being considered a global epidemic. A growing body of evidence highlights the relevance of inflammasomes as a consequence of metabolic disorders and obesity. NLRP3 is the most studied component of the inflammasomes. Gut microbes contribute to the subclinical systemic inflammation that ultimately leads to the development of pathologies such as obesity, insulin resistance. Therefore, the use of intestinal microbiota modulators (e.g probitoics, prebiotics, or both as synbiotics) may improve several metabolic and immune functions. Recently, the link between these modulators and NLRP3 in obesity is less investigated. Aim of the Work to study the potential involvement of inflammasomes as an indicator for the efficacy of synbiotics in alleviating diet-induced obesity. Materials and Methods Thirty adult male Wistar rats were randomly divided into four groups (7 rats /group): normal control group (receiving normal diet), HFD (high fat diet) group, normal group receiving synbiotics, and HFD rats receiving synbiotics. After eight weeks, all rats were sacrificed then WAT (visceral, subcutaneous), brown adipose tissue, and liver were obtained. The body weight of each rat was measured weekly. The expression of NLRP3 was performed by real-time PCR. Results HFD induced a significant weight gain compared to normal diet (p < 0.05). However, synbiotics administration could not affect such weight gain in rats receiving HFD with synbiotics (p > 0.05). The expression of NLRP3, pre-inflammatory marker, is elevated in adipose and liver tissues in HFD group compared to normal diet group (p < 0.05). However, synbiotics successfully reduced the expression of NLRP3 in all previous tissues (p < 0.05). Conclusion the intake of synbiotics could disrupt the inflammatory consequences of obesity through targeting the expression of NLRP3. Thereby, synbiotics might be a promising potential therapeutic agent in treatment of obesity.