Objective <p>Irisin is a myokine that is secreted by muscle tissue and is recognized for its regulatory effects on inflammation. The objective of this study was to examine the potential anti-inflammatory function of irisin in the context of colon cancer, with a focus on its effects on the Caco-2 cell line. Method: Specifically, pro-inflammatory cytokine levels (IL-6 and TNF-α), apoptotic marker Caspase-3 activity, and changes in the NF-κB signaling pathway were assessed using ELISA assays.</p> Results <p>The findings of this study indicated a substantial augmentation in IL-6 levels in the 100 nM irisin-treated group in comparison to the control group (<i>p</i> &lt; 0.05). Furthermore, a significant divergence in Caspase-3 activity was observed between the 10 nM and 100 nM irisin groups (<i>p</i> &lt; 0.05). While direct antiproliferative effects of irisin on Caco-2 cells were not evident in analyses of cellular toxicity, a significant increase in Caspase-3 activity suggested activation of apoptotic pathways. Furthermore, the upregulation of NF-κB signaling, which is generally linked to cancer progression through the suppression of apoptosis, was observed following irisin treatment.</p> Conclusion <p>Irisin did not exert a consistent antiproliferative effect in Caco-2 cells under the tested conditions. Instead, irisin exposure was associated with alterations in inflammatory and apoptotic markers, including increased IL-6 and NF-κB levels and modulation of caspase-3 activity. These findings suggest that irisin may act as a context-dependent regulator of inflammatory and apoptotic signaling rather than a direct anti-inflammatory or antiproliferative agent in colon cancer cells.</p>