Curcumin was demonstrated to be an active ingredient with anti-inflammatory effects. This research was to investigate the effects of curcumin. We found that curcumin promoted cell viability and suppressed cell apoptosis. Meanwhile, curcumin decreased the level of cleaved caspase-3 and the release of TNF-alpha, IL-1 beta, IL-6, but increased IL-10 release in LPS-treated BV2 cells. miR-362-3p expression was upregulated by curcumin, while TLR4 expression was downregulated. Besides, we observed that the cytoprotective effects of curcumin were lost when miR-362-3p was silenced. TLR4 was a direct target gene of miR-362-3p. Moreover, miR-362-3p deletion attenuated the cytoprotective effects of curcumin by regulating TLR4 expression in LPS-induced BV2 cells. Furthermore, curcumin suppressed p-p65 expression via regulating miR-362-3p/TLR4 axis. We discovered that curcumin exhibited protective effects against LPS-triggered cell injury via modulating miR-362-3p/TLR4 axis through NF-kappa B pathway.